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CompletedNCT04326478Updated Aug 7, 2026Results posted

Single Dose Azithromycin to Prevent Cholera in Children

A Phase 2 interventional study of Azithromycin and Placebo in Cholera, sponsored by Massachusetts General Hospital. Completed at 1 site in Bangladesh. Open to participants aged 1 Year to 15 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-08-07.

Sponsored by Massachusetts General Hospital · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
2,475
Allocation
Randomized
Ages
1 Year to 15 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Cholera

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Keywords

  • Cholera
  • Child Health
03

Who can participate

Ages eligible
1 Year to 15 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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
04

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
2,475 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Azithromycin

  • Placebo comparator
    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.

    Biological: Placebo

Interventions

  • DrugAzithromycin

    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.

  • BiologicalPlacebo

    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.

05

What researchers measure

Primary outcomes

  1. Rate of V. Cholerae Infection in Household Contacts of Cholera Index Cases

    The presence of V. cholerae O1 will be determined via the culturing of specimens collected via rectal swab sampling. Rectal swab acquisition will begin on the day of azithromycin administration and repeat on days 2, 3, 5, 6, and 7 following the intervention.

    Time frame: 1 week

06

Results

Posted Aug 7, 2026

Participant flow

Participants were recruited from households of index patients with culture-confirmed cholera in Dhaka, Bangladesh. Eligible participants were household child contacts 1 to 15 years of age.

Participant flow — Overall Study
MilestoneAzithromycinPlacebo
Started314313
Completed314313
Not completed00

Outcome measures

PrimaryRate of V. Cholerae Infection in Household Contacts of Cholera Index Cases

The presence of V. cholerae O1 will be determined via the culturing of specimens collected via rectal swab sampling. Rectal swab acquisition will begin on the day of azithromycin administration and repeat on days 2, 3, 5, 6, and 7 following the intervention.

Time frame:
1 week
Reported as:
Count of participants · Participants
Rate of V. Cholerae Infection in Household Contacts of Cholera Index Cases
ParticipantsAzithromycinPlacebo
Culture positive, ITT2767
Culture negative, ITT287246
Statistical analysis
  • Azithromycin vs Placebo · Regression, Cox · p = <0.001 · Hazard ratio (hr): 0.41 · 95% CI 0.25 to 0.68

Adverse events

Collected over 6 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Azithromycin Group0/314 (0%)0/314 (0%)0/314 (0%)
Non-antibiotic Placebo Group0/313 (0%)1/313 (0.3%)0/313 (0%)
Most frequent serious events
Most frequent serious events
EventAzithromycin GroupNon-antibiotic Placebo Group
HospitalizationInfections and infestations0/3141/313

Baseline characteristics

Only household contacts assigned to an intervention - not screened and index patients

Age, Categorical
Age, Categorical(Participants)AzithromycinPlaceboTotal
<=18 years314313627
Between 18 and 65 years000
>=65 years000
Sex: Female, Male
Sex: Female, Male(Participants)AzithromycinPlaceboTotal
Female146158304
Male168155323
Race (NIH/OMB)
Race (NIH/OMB)(Participants)AzithromycinPlaceboTotal
American Indian or Alaska Native000
Asian314313627
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(Participants)AzithromycinPlaceboTotal
Bangladesh314313627
Participants Assigned an Intervention
Participants Assigned an Intervention(Participants)AzithromycinPlaceboTotal
Count of participants314313627
07

Study locations

1 site
  • icddr,b Dhaka hospital
    Dhaka, Bangladesh
08

References and documents

Study documents

  • Protocol, analysis plan and consent form · Jan 26, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT04326478
Lead sponsor
Massachusetts General Hospital
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
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, Massachusetts General Hospital) — Principal investigator
First posted
Mar 30, 2020
Start date
Oct 31, 2021
Primary completion
May 31, 2025
Completion
May 31, 2025
Results posted
Aug 7, 2026
Last update
Aug 7, 2026

Study contacts

Jason B Harris, MD, MPH
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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