MORDOR II Burkina Faso: Longitudinal Trial

NCT03676751 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: OPP1187628-C
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Globally, childhood mortality has shown a promising downward trend in recent years, however, many sub-Saharan countries still have relatively high child mortality rates. In previous studies within Niger, Tanzania, and Malawi, mass azithromycin treatment to children aged 1-59 months old effectively reduced all-cause childhood mortality. A similar study will be conducted in Burkina Faso to replicate the results of mass azithromycin treatment. The investigators propose an individually randomized placebo-controlled trial alongside the MORDOR II Burkina Faso trial 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. Many questions surround the mechanism behind azithromycin's effect on reducing childhood mortality. Further questions exist regarding antibiotic resistance and how mass antibiotic administration can impact intestinal microflora. The goal of this study is to demonstrate the changes in the gut microbiome after antibiotic administration and to measure the growth of children after receiving a single dose of azithromycin. Additionally we will measure resistance markers, inflammatory markers, and IgA-bound bacteria. We hypothesize that a single dose of azithromycin will lead to a significant increase in child growth and that the gut microbiome will be significantly different in children who received azithromycin compared to those who received placebo. Objectives:

1. 1.. To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on longitudinal changes in the intestinal microbiome over a 6-month period. We hypothesize that a single dose of azithromycin will result in a significant difference in the intestinal microbiome within the treatment group compared to the placebo group after a 6-month period within children ages 8 days-59 months.
2. 2.. To determine the effect of a single dose of azithromycin for children aged 8 days-59 months on child growth over a 6-month period. We hypothesize that a single dose of azithromycin will increase child growth over a 6-month period in children aged 8 days-59 months.
3. 3.. To determine the effect of a single dose of azithromycin for children aged 8 days to 59 months on the presence of macrolide genetic resistance determinants within the first two weeks post-treatment. The investigators hypothesize that a single dose of azithromycin will increase the presence of macrolide resistance determinants over a 2 week period in children aged 8 days to 59 months.

Conditions

Child Growth; Diversity of Microbiome; Child Mortality; Resistance Bacterial

Keywords

azithromycin; mass drug administration; childhood mortality

Outcome Measures

Primary Outcomes (2)

• Intestinal Microbial Diversity

  The primary outcome of the study was pre-specified as α-diversity (inverse Simpson's) at the genus level, expressed in effective number. The minimum of Simpson's index of diversity is 0, there is no maximum. Higher Simpson's index of diversity means more diverse. There are no subscales.

  6 months

• Macrolide Resistance

  Presence of macrolide genetic resistance determinants measured using DNA-seq from rectal swabs from 450 children. Macrolide resistance is defined by resistance to erythromycin or clarithromycin. We compare the read numbers of macrolide resistance in each treatment group. A higher read number indicates more resistance.

  2 weeks

Secondary Outcomes (15)

• Change in Weight Over Time

  180 days post-treatment

• Change in Height Over Time

  180 days post-treatment

• Number of Participants With Infantile Hypertrophic Pyloric Stenosis

  6 months

• Mortality

  180 days post-treatment

• Malaria Status

  180 days post-treatment

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

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

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Azithromycin 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.

Azithromycin

Placebo DRUG

Oral suspension of placebo for azithromycin

Placebo

Eligibility Criteria

• Age: 8 Days - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• \<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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Centre de Recherche en Sante de Nouna, Burkina Faso: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Centre de Recherche en Sante de Nouna

Nouna, Burkina Faso

Location

Related Publications (4)

• Doan T, Liu Z, Sie A, Dah C, Bountogo M, Ouattara M, Coulibaly B, Kiemde D, Zonou G, Nebie E, Brogdon J, Lebas E, Hinterwirth A, Zhong L, Chen C, Zhou Z, Porco T, Arnold BF, Oldenburg CE, Lietman TM. Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial. Am J Trop Med Hyg. 2024 Jan 16;110(2):291-294. doi: 10.4269/ajtmh.23-0651. Print 2024 Feb 7.

  PMID: 38227963 DERIVED

• Coulibaly B, Kiemde D, Zonou G, Sie A, Dah C, Bountogo M, Brogdon J, Hu H, Lebas E, Porco TC, Doan T, Lietman TM, Oldenburg CE. Effect of Single-dose Azithromycin on Pneumococcal Carriage and Resistance: A Randomized Controlled Trial. Pediatr Infect Dis J. 2022 Sep 1;41(9):728-730. doi: 10.1097/INF.0000000000003585. Epub 2022 May 23.

  PMID: 35944061 DERIVED

• Coulibaly B, Sie A, Dah C, Bountogo M, Ouattara M, Compaore A, Nikiema M, Tiansi JN, Sibiri ND, Brogdon JM, Lebas E, Doan T, Porco TC, Lietman TM, Oldenburg CE. Effect of a single dose of oral azithromycin on malaria parasitaemia in children: a randomized controlled trial. Malar J. 2021 Aug 31;20(1):360. doi: 10.1186/s12936-021-03895-9.

  PMID: 34465327 DERIVED

• Sie A, Coulibaly B, Dah C, Bountogo M, Ouattara M, Compaore G, Brogdon JM, Godwin WW, Lebas E, Doan T, Arnold BF, Porco TC, Lietman TM, Oldenburg CE. Single-dose azithromycin for child growth in Burkina Faso: a randomized controlled trial. BMC Pediatr. 2021 Mar 17;21(1):130. doi: 10.1186/s12887-021-02601-7.

  PMID: 33731058 DERIVED

MeSH Terms

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Pr Thomas Lietman
• Organization: UCSF FI Proctor

tom.lietman@ucsf.edu

(415) 476-1442

Study Officials

• Catherine Oldenburg, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Ali Sie, MD, PhD

  Centre de Recherce en Sante de Nouna

  PRINCIPAL INVESTIGATOR

• Tom Lietman, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple: (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Individually randomized placebo-controlled trail of azithromycin vs. placebo to establish the efficacy and safety of azithromycin.

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 19, 2018
• Study Start: October 10, 2019
• Primary Completion: July 6, 2020
• Study Completion: July 6, 2020
• Last Updated: August 9, 2023
• Results First Posted: August 9, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)