Clinical trial NCT04326478: Single Dose Azithromycin to Prevent Cholera in Children
Official title: Azithromycin Prophylaxis in Child Contacts of Cholera Patients: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Cholera
Keywords: Cholera
Child Health
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2020-03-30
Enrollment: 920
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Each household will be randomized to either receive a single-dose of azithromycin or receive non-antibiotic placebo. All study visits after the drug administration, which occurs during the first visit, are equal for both groups.
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Rate of V. cholerae infection in household contacts of cholera index cases
timeFrame: 57 months after enrollment of first subject
Secondary outcomes:
measure: Duration of V. cholerae shedding
timeFrame: 50 months after enrollment of first subject
measure: Presence of any antibiotic or its metabolite detected by liquid chromatography-mass spectrometry (LC/MS) in the stool, beyond the assigned azithromycin intervention
timeFrame: 50 months after enrollment of first subject
measure: Rate of acquisition of antibiotic resistance following azithromycin treatment
timeFrame: 50 months after enrollment of first subject
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: icddr,b Dhaka hospital
Study officials:
affiliation: Massachusetts General Hospital
name: Jason B Harris, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: