Gut and Azithromycin Mechanisms in Infants and Children II

NCT ID: NCT04315272

Last Updated: 2023-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 449 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-21
• Study Completion Date: 2022-06-01

Brief Summary

Childhood mortality is decreasing worldwide. However, many sub-Saharan countries still have high children under 5 mortality rates. The MORDOR trial in Niger, Tanzania, and Malawi demonstrated a near 14% decrease in all-cause child mortality following biannual azithromycin in children 1-59 months. Current trials in Burkina aim to replicate these results from the MORDOR study with mass azithromycin treatment.

The investigators conducted an individually randomized placebo-controlled trial in Burkina Faso called the Gut and Azithromycin Mechanisms in Infants and Neonates Trial (GAMIN: NCT03676751) to evaluate the effect of a single dose of azithromycin (20 mg/kg) on potential mediators of the effect of azithromycin on all-cause mortality and to evaluate changes in the gut microbiome longitudinally (results pending). Here, the investigators propose to conduct an expansion of the original GAMIN trial. In GAMIN II, the investigators will evaluate 450 additional 1-59 month old children longitudinally for 6 months with a focus on stool collection and malaria status.

Objectives:

1. To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on malaria. The investigators hypothesize that a single dose of azithromycin will result in a reduced malaria status within the treatment group compared to the placebo group after a 14 day period within children ages 8 days-59 months.

The study will be conducted in Nouna Town in northwestern Burkina Faso.

Detailed Description

The investigators' previous MORDOR I research demonstrated a significant reduction in all-cause child mortality after biannual mass azithromycin distribution. In three sub-Saharan Africa countries, (including Niger, Tanzania, and Malawi) mass azithromycin treatment over 2 years resulted in a 14% reduction in child mortality. Moreover, 1 in 5-6 deaths were shown to be averted within Niger alone1. Similar findings were demonstrated in a previous study for trachoma control in Ethiopia with mass azithromycin distribution. This study in rural Ethiopia noted a nearly 50% decrease in all-cause childhood mortality5. However, neither of these studies evaluated the longitudinal impact azithromycin has on the gut microbiome. The MORDOR II trial in Burkina Faso will further evaluate the efficacy of biannual azithromycin treatment. The under-5 child mortality rate in Burkina Faso is approximately 110 per 1,000 live births. Major causes of child mortality in this area are infectious mostly due to malaria, diarrhea, and upper respiratory tract infections. In addition, malnutrition contributes to a high burden of child mortality and morbidity within this region as well. By treating underlying conditions, the use of routine antibiotic treatment could reduce diverse health outcomes leading to morbidity and mortality. The investigative team proposes to conduct this study alongside the MORDOR II trial in the town of Nouna where a majority of childhood deaths are attributable to infectious causes and malnutrition.

The World Health Organization is considering adopting the presumptive use of azithromycin and other antibiotics as a recommendation to reduce childhood mortality in areas with a high infectious disease burden. Many questions remain unanswered surrounding the use of mass antibiotic treatment in areas with high child morbidity and mortality. This study will add to the current knowledge of mass azithromycin distribution from our previous MORDOR I research. The investigators propose to evaluate how azithromycin will impact childhood growth and to assess the changes that occur in the intestinal microbiome following a single dose of azithromycin treatment. The goal is to contribute more scientific literature that could assist future guidelines regarding antibiotic use.

The role of antibiotics on the gut microflora is unclear. Longitudinal studies have been recommended to further investigate the role of antibiotics on the microbiome. The investigators propose a longitudinal study designed to improve our knowledge about the changes in the intestinal microbiome following the course of a single dose of antibiotic in a setting with high childhood mortality and morbidity. More specifically, the investigators propose to follow 450 children for a 6-month time period that are between the ages of 8 days old and 59 months old. Children in this age bracket are at the highest risk for mortality from infectious causes, and furthermore, they are at the highest risk for malnutrition. This group of children would receive the greatest benefit from this intervention. The causal changes in the microbiome are vastly understudied in regards to changes in the gut microbiome following a course of antibiotics. Additionally, this study will provide valuable data on the effect of azithromycin for malaria status within 2 weeks of treatment.

Conditions

Malaria

Study Design

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

Study Groups

Azithromycin

A single dose of azithromycin will be administered to children between the ages of 8 days and 59 months old.

Group Type: ACTIVE_COMPARATOR

Azithromycin

Intervention Type: DRUG

Zithromax® for oral suspension is supplied in bottles containing azithromycin dehydrate powder equivalent to 1200mg per bottle and the following inactive ingredients: sucrose; tribasic anhydrous sodium phosphate; hydroxypropyl cellulose; xanthan gum; FD\&C Red #40; and flavoring including spray dried artificial cherry, crème de vanilla, and banana. After constitution, a 5mL suspension contains 200mg of azithromycin.

Placebo

A single dose of placebo will be administered to children between the ages of 8 days and 59 months old.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Azithromycin

Zithromax® for oral suspension is supplied in bottles containing azithromycin dehydrate powder equivalent to 1200mg per bottle and the following inactive ingredients: sucrose; tribasic anhydrous sodium phosphate; hydroxypropyl cellulose; xanthan gum; FD\&C Red #40; and flavoring including spray dried artificial cherry, crème de vanilla, and banana. After constitution, a 5mL suspension contains 200mg of azithromycin.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Zithromax

Eligibility Criteria

Inclusion Criteria

• Between 8 days and 59 months old
• Primary residence within catchment area of study site
• Available for full 6 month study
• No known allergy to macrolides/azalides
• Appropriate written informed consent from at least one parent or guardian
• Able to feed orally

Exclusion Criteria

• <8 days old or >59 months
• Primary residence outside catchment area of study site
• Not available for full 6 month study
• Known allergy to macrolides/azalides
• No written informed consent from at least one parent or guardian
• Unable to feed orally

• Minimum Eligible Age: 8 Days
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre de Recherche en Sante de Nouna, Burkina Faso

OTHER_GOV

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catie Oldenburg, ScD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

Centre de Recherche en santé de nouna

Nouna, Boucle du Mouhoun, Burkina Faso

Countries

Burkina Faso

References

Brogdon J, Dah C, Sie A, Bountogo M, Coulibaly B, Kouanda I, Ouattara M, Compaore G, Nebie E, Seynou M, Lebas E, Nyatigo F, Hu H, Arnold BF, Lietman TM, Oldenburg CE. Malaria positivity following a single oral dose of azithromycin among children in Burkina Faso: a randomized controlled trial. BMC Infect Dis. 2022 Mar 25;22(1):285. doi: 10.1186/s12879-022-07296-4.

Reference Type: DERIVED

PMID: 35337289 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

OPP1187628-D

Identifier Type: -

Identifier Source: org_study_id