Child GrowthPhase 4GAMINNCT03676751
MORDOR II Burkina Faso: Longitudinal Trial
A Phase 4 study testing Azithromycin in people with Child Growth and Diversity of Microbiome, run by University of California, San Francisco at 1 site in Burkina Faso.
Trial 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… Read more about this study
- Who is it for?
- Ages 8 days to 59 monthsHealthy volunteers can take part
- Conditions the study is for
- Child Growth, Diversity of Microbiome, Child Mortality
- What is being tested?
- Azithromycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- 1 siteBurkina Faso
- Study dates
- 10 Oct 2019to 6 Jul 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 days to 59 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- <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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Gut and Azithromycin Mechanisms in Infants and Neonates
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.
Read more
Objectives:
- . 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.
- . 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.
- . 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.
The study will be conducted in Nouna Town in northwestern Burkina Faso.
Read the 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 burden2. 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 child growth is unclear. Recent studies indicate that antibiotic use could impact child growth, but a previous study in Niger failed to find a statistically significant correlation between antibiotic treatment with azithromycin and stunting, underweight, or MUAC of pre-school aged children. Longitudinal studies have been recommended to further investigate the role of antibiotics on child growth6. Meanwhile some studies suggest antibiotics may create modifications in the gut microbiota impacting nutrient absorption and weight gain7.The investigative team proposes to measure child growth through anthropometric measurements longitudinally over a 6-month period to see if azithromycin treatment impacts child development. We hypothesize that children receiving a dose of azithromycin will have more growth and development in terms of height, weight, and mid-upper arm circumference compared to children who receive placebo.
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, we propose to follow 500 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. The investigators hypothesize that children receiving a dose of azithromycin will have a higher prevalence of pneumococcal resistance in nasopharyngeal samples, decreased bacterial diversity, and a higher likelihood of identification of bacterial resistance genes in stool and nasopharyngeal samples.
A small group of 50 children (25 per arm) will be followed more intensely within the first 2 weeks of treatment to evaluate macrolide resistance. The investigators hypothesize that children receiving azithromycin will have a greater presence of macrolide genetic resistant determinants.
- Being tested
- Azithromycin, Placebo
- Keywords
- azithromycin, mass drug administration, childhood mortality
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
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.
PlaceboDrug
Oral suspension of placebo for azithromycin
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin | Active comparator | A single dose of azithromycin will be administered to children between the ages of 8 days and 59 months old. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 weeks
Secondary outcomes (15)
Change in Weight Over Time
WAZ. Weight will be measured at all follow-ups and weight-for-age z-scores will be calculated. Weight measured in kg.
Measured: 180 days post-treatment
Change in Height Over Time
Height or length will be measured at all follow-ups and height-for-age z-scores will be calculated.
Measured: 180 days post-treatment
Number of Participants With Infantile Hypertrophic Pyloric Stenosis
Measured: 6 months
Mortality
Vital status will be assessed at all follow-up time points. Mortality will be defined as death within the study period. Date of death will be collected.
Measured: 180 days post-treatment
Malaria Status
Number of Participants Positive for Malaria. Blood smears (thin and thick) for malaria will be collected at all follow-ups to determine malaria infection status.
Measured: 180 days post-treatment
Adverse Events
Caregivers will be asked if the child has been taken to the health post since the last visit and why
Measured: 14 days post-treatment
Genotypic Resistance
Total resistance read numbers in 12 classes: Aminoglycosides, Cationic antimicrobial peptides, Elfamycins, MLS, Metronidazole, Multi-drug resistance, Phenicol, Rifampin, Sulfonamides, Tetracyclines, Trimethoprim, and Beta-lactams.
We compare the read numbers of macrolide resistance in each treatment group. A higher read number indicates more resistance.
Measured: 180 days post-treatment
Inflammatory Marker Changes
Measured by C-reactive protein
Measured: 6 months
IgA-bound Bacteria From Small Intestine Changes
Measured using BugFACS from whole blood and stool
Measured: 180 days post-treatment
Nutritional Status
To be measured using mid-upper arm circumference
Measured: 180 days post-treatment
Acute Modulation of the Gut Microbiome
Next generation sequencing
Measured: 2 weeks post-treatment
L-1 Norm Distance on Bacterial Reads (Intestinal)
L-1 norm distance on bacterial reads (intestinal) from rectal swabs of 50 children. L1-norm distance on bacterial reads (intestinal) - L1 norm is equivalent to Shannon's diversity. Shannon's Alpha Diversity combines richness and diversity. Shannon's index of diversity (alpha diversity) measures both the number of species and the inequality between species abundances. A large value is given by the presence of many species with well balanced abundances.
Measured: 2 weeks post-treatment
L-2 Norm Distance on Bacterial Reads (Intestinal)
L-2 norm distance on bacterial reads (intestinal) from rectal swabs of 450 children. L2-norm distance on bacterial reads (intestinal) - L2 norm is equivalent to Simpson's diversity. Simpson's Alpha Diversity were obtained at Baseline and Post-treatment in this study. 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.
Measured: 2 weeks post-treatment
Changes in Normalized Reads for Campylobacter Species
Reduce in normalized reads for Campylobacter species using DNA-seq from rectal swabs of 450 children.
We compare the read numbers of Campylobacter species in each treatment group. Campylobacter is associated with disease. Reduction in Campylobacter species burden may reduce diarrhea-related mortality.
Measured: 2 weeks post-treatment
Resistome
Chao1 total resistance gene determinant richness using DNA-seq from rectal swabs of 450 children.
We calculated Chao1 total resistance gene determinant richness across arms. Species richness is the simplest measure of biodiversity and is just a count of the number of different species in a given area.
Measured: 2 weeks post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2018
- Study start10 Oct 2019
- Primary completion6 Jul 2020
- Study completion6 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Child GrowthStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Individually randomized placebo-controlled trail of azithromycin vs. placebo to establish the efficacy and safety of azithromycin.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso, Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Catherine Oldenburg, PhD, Principal investigator, University of California, San FranciscoAli Sie, MD, PhD, Principal investigator, Centre de Recherce en Sante de NounaTom Lietman, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03676751
- Sponsor's protocol ID
- OPP1187628-C
- Acronym
- GAMIN
- Status last verified
- Jul 2023
- First submitted
- 17 Sep 2018
- Last updated
- 9 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38227963Coulibaly 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.
PubMed 35944061Coulibaly 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.
PubMed 34465327Sie 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.
PubMed 33731058
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gut and Azithromycin Mechanisms in Infants and Neonates
- ClinicalTrials.gov ID
- NCT03676751
- Acronym / sponsor ID
- GAMIN / OPP1187628-C
- Keywords
- azithromycin, mass drug administration, childhood mortality
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Centre de Recherche en Sante de Nouna, Burkina Faso, Bill and Melinda Gates Foundation
- Study start
- 10 Oct 2019 (actual)
- Primary completion
- 6 Jul 2020 (actual)
- Study completion
- 6 Jul 2020 (actual)
- First posted
- 19 Sep 2018 (actual)
- Results
- Posted 9 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- . 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.
- . 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.
- . 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.
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 burden2. 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 child growth is unclear. Recent studies indicate that antibiotic use could impact child growth, but a previous study in Niger failed to find a statistically significant correlation between antibiotic treatment with azithromycin and stunting, underweight, or MUAC of pre-school aged children. Longitudinal studies have been recommended to further investigate the role of antibiotics on child growth6. Meanwhile some studies suggest antibiotics may create modifications in the gut microbiota impacting nutrient absorption and weight gain7.The investigative team proposes to measure child growth through anthropometric measurements longitudinally over a 6-month period to see if azithromycin treatment impacts child development. We hypothesize that children receiving a dose of azithromycin will have more growth and development in terms of height, weight, and mid-upper arm circumference compared to children who receive placebo.
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, we propose to follow 500 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. The investigators hypothesize that children receiving a dose of azithromycin will have a higher prevalence of pneumococcal resistance in nasopharyngeal samples, decreased bacterial diversity, and a higher likelihood of identification of bacterial resistance genes in stool and nasopharyngeal samples.
A small group of 50 children (25 per arm) will be followed more intensely within the first 2 weeks of treatment to evaluate macrolide resistance. The investigators hypothesize that children receiving azithromycin will have a greater presence of macrolide genetic resistant determinants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Individually randomized placebo-controlled trail of azithromycin vs. placebo to establish the efficacy and safety of azithromycin.
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Active comparator | Drug: AzithromycinA single dose of azithromycin will be administered to children between the ages of 8 days and 59 months old. |
| Placebo | Placebo comparator | Drug: PlaceboA single dose of placebo will be administered to children between the ages of 8 days and 59 months old. |
Who may qualify
- Ages
- 8 days to 59 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- <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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinZithromax® 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. | Drug | Azithromycin |
| PlaceboOral suspension of placebo for azithromycin | Drug | Placebo |
Primary outcome
Intestinal Microbial Diversity
Time frame: 6 months
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.
Macrolide Resistance
Time frame: 2 weeks
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.
15 secondary outcomes
Change in Weight Over Time
Time frame: 180 days post-treatment
Change in Height Over Time
Time frame: 180 days post-treatment
Number of Participants With Infantile Hypertrophic Pyloric Stenosis
Time frame: 6 months
Mortality
Time frame: 180 days post-treatment
Malaria Status
Time frame: 180 days post-treatment
Adverse Events
Time frame: 14 days post-treatment
Genotypic Resistance
Time frame: 180 days post-treatment
Inflammatory Marker Changes
Time frame: 6 months
IgA-bound Bacteria From Small Intestine Changes
Time frame: 180 days post-treatment
Nutritional Status
Time frame: 180 days post-treatment
Acute Modulation of the Gut Microbiome
Time frame: 2 weeks post-treatment
L-1 Norm Distance on Bacterial Reads (Intestinal)
Time frame: 2 weeks post-treatment
L-2 Norm Distance on Bacterial Reads (Intestinal)
Time frame: 2 weeks post-treatment
Changes in Normalized Reads for Campylobacter Species
Time frame: 2 weeks post-treatment
Resistome
Time frame: 2 weeks post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38227963Doan 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.
- Derived from this study: PubMed 35944061Coulibaly 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.
- Derived from this study: PubMed 34465327Coulibaly 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.
- Derived from this study: PubMed 33731058Sie 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Oldenburg, PhD principal investigator
University of California, San Francisco
Ali Sie, MD, PhD principal investigator
Centre de Recherce en Sante de Nouna
Tom Lietman, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin in people with Child Growth and Diversity of Microbiome, run by University of California, San Francisco at 1 site in Burkina Faso.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Burkina Faso. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intestinal Microbial Diversity (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03676751, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023.