Single Dose Azithromycin to Prevent Cholera in Children

NCT ID: NCT04326478

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 920 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-31
• Study Completion Date: 2026-05-31

Brief Summary

This study aims to determine whether single-dose azithromycin is effective in preventing cholera in children who are at extremely high risk of infection. The study will also determine the effect of this intervention on the development of antibiotic resistant bacteria. The results will inform future strategies to prevent cholera in children, and improve overall understanding of the impact of azithromycin on antibiotic resistance.

Detailed Description

Vibrio cholerae causes 3 million cases of cholera and 100,000 deaths annually. An ongoing epidemic in Yemen has caused 1.7 million cases of cholera, with 58% of cholera-related deaths occurring in children. The World Health Organization (WHO) has targeted the elimination of cholera transmission by the year 2030, but the increasing burden of cholera suggests that more effective approaches are needed to prevent the disease. Access to safe water and sanitation and the use of oral cholera vaccines (OCV) are central to the WHO-proposed approach, but children remain particularly vulnerable. Children are at the highest risk of severe disease, and current cholera vaccines are ineffective in young children. In addition, natural disasters and human conflict often delay vaccination and other large-scale interventions.

Effective antibiotics reduce the volume and duration of diarrhea in cholera by over 50% and bacterial shedding by 80%. They are recommended for the treatment of moderate to severe cholera. Due to limited data, there are no standards for the use of antibiotic prophylaxis for cholera, resulting in widely varied clinical practices and the frequent use of antibiotics with unproven efficacy. For this reason, the WHO Global Task Force on Cholera Control has prioritized research in this area, suggesting that further use of prophylactic antibiotics for cholera should be stopped until prospective studies designed to measure the effectiveness of antibiotic prophylaxis and its impact on antibiotic resistance can be conducted. This study will address these two knowledge gaps. This study will determine whether a single dose of azithromycin is effective in preventing V. cholerae infection in children, and evaluate the impact of its administration on antibiotic resistance in the gut. This study focuses on children because current OCVs are ineffective in young children and because children are at the highest risk of infection and mortality from cholera. While single-dose azithromycin is a preferred treatment for cholera, it has never been studied as prophylaxis. Azithromycin has also been shown to be safe and beneficial in other recent chemoprophylaxis studies in children.

This is a double-blinded cluster randomized clinical trial of single-dose azithromycin to prevent cholera in children who are household contacts of a patient with cholera in Dhaka, Bangladesh. 920 children ages 1-15 years from 400 households in Dhaka, Bangladesh, who have shared cooking facilities for the prior three days with a household member with moderate to severe V. cholerae O1 infection, can participate in this study.

Conditions

Cholera

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Azithromycin Group

Enrolled children in a household randomized to the experimental group will receive a single weight-based dose of azithromycin administered by a trained study nurse within 12 hours of a member of their household testing positive for cholera. They will then complete 9 follow-up study visits in their home, during which rectal swabs and/or stool samples will be collected.

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

Enrolled children in the intervention arm of this study will receive a single weight-based dose of azithromycin (20 mg/kg, to a maximum dose of 1 gram) administered by a trained study nurse within 12 hours of a member of their household testing positive for cholera.

Non-antibiotic Placebo Group

Enrolled children in a household randomized to the placebo arm will receive a single dose of non-antibiotic placebo during their first study visit, which will occur within 12 hours of a member of their household testing positive for cholera. Like the participants in the intervention arm, they will complete 9 follow-up study visits in their home, during which rectal swabs and/or stool samples will be collected.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Enrolled children in the placebo arm of this study will receive a single dose of non-antibiotic placebo administered by a trained study nurse within 12 hours of a member of their household testing positive for cholera.

Interventions

Azithromycin

Enrolled children in the intervention arm of this study will receive a single weight-based dose of azithromycin (20 mg/kg, to a maximum dose of 1 gram) administered by a trained study nurse within 12 hours of a member of their household testing positive for cholera.

Intervention Type: DRUG

Placebo

Enrolled children in the placebo arm of this study will receive a single dose of non-antibiotic placebo administered by a trained study nurse within 12 hours of a member of their household testing positive for cholera.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Shared cooking facilities for the prior three days with a household member who tested positive for cholera
• Age 1 to 15 years
• A parent or guardian available to provide informed consent
• Intention to remain enrolled in the study for 6 months

Exclusion Criteria

• Participation in any other drug, device, or vaccine trial at present or within the past 30 days
• Known or suspected hypersensitivity to azithromycin or other macrolide antibiotics

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

International Centre for Diarrhoeal Disease Research, Bangladesh

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jason B. Harris, MD

Chief, Division of Pediatric Global Health, Associate Professor of Pediatrics, Harvard Medical School, Attending, Pediatric Infectious Diseases, Microbiology, Massachusetts General Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason B Harris, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

icddr,b Dhaka hospital

Dhaka, , Bangladesh

Countries

Bangladesh

Other Identifiers

2020P000457

Identifier Type: -

Identifier Source: org_study_id