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Childhood MortalityPhase 4NAITRENCT03682653

Neonates and Azithromycin, an Innovation in the Treatment of Children in Burkina Faso

A Phase 4 study testing Azithromycin in people with Childhood Mortality, run by University of California, San Francisco at 1 site in Burkina Faso.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Although under-5 mortality rates are declining globally, neonatal mortality remains persistently high in many regions of sub-Saharan Africa. Mass azithromycin distribution to children aged 1-59 months has been shown to reduce childhood mortality in Niger, Tanzania, and Malawi. Read more about this study

Who is it for?
Ages 8 to 27 daysHealthy volunteers can take part
Conditions the study is for
Childhood Mortality
What is being tested?
Azithromycin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21,832 participants
Where
1 siteBurkina Faso
Study dates
11 Apr 2019to 31 Dec 2022
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 to 27 days
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • Within 4 hours of a facility that can provide services for pyloromyotomy (Ouagadougou or Bobo Dioulasso)
  • Accessible during the rainy season
  • Ultrasound machine available OR a facility in which an ultrasound machine could be placed is within 1 hour
  • Weight over 2500 g
  • Able to feed orally
  • Family intends to stay in study area for at least 6 months
Show all 10Show fewer
  • Appropriate consent from at least one caregiver
  • No known allergy to azalides
  • Not living within one of the communities included in the community study(CHAT/CHATON)
  • No hepatic failure manifested by neonatal jaundice

Who cannot join

  • Refusal of village chief
  • Individuals:
  • Weight <2500 g
  • Unable to feed orally
  • Family planning to move
  • Mother/caregiver not willing to participate
Show all 9Show fewer
  • Allergic to azalides
  • Living in one of the communities included in the community study (CHAT/CHATON)
  • Hepatic failure manifested by neonatal jaundice

Trial locations and contacts

1 site in 1 country.

Burkina Faso1 site
  • Centre de Recherche En Santé de Nouna

    Nouna, BP 02

Other trials in Burkina Faso

About this study

Although under-5 mortality rates are declining globally, neonatal mortality remains persistently high in many regions of sub-Saharan Africa. Mass azithromycin distribution to children aged 1-59 months has been shown to reduce childhood mortality in Niger, Tanzania, and Malawi. This study did not evaluate the effect of azithromycin administered during the neonatal period. Observational evidence from high income countries has suggested that macrolides, including erythromycin and azithromycin, may be associated with increased risk of development of infantile hypertrophic pyloric stenosis (IHPS). However, these studies are limited by confounding by indication, as infants only receive antibiotics when they are ill.

The investigators proposed an individually randomized trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period. The long-term goal is generate evidence that can be used by neonatal and child survival programs related to the use of azithromycin in the youngest children who have the highest risk of mortality. The investigators hypothesize that a single dose of azithromycin administered in the neonatal period will lead to significantly reduced risk of mortality and that this dose will be safe.

Read more

Objectives

  1. Establish the efficacy of a single dose of azithromycin administered during the neonatal period compared to placebo in infants 8 to 27 days of life for reduction in all-cause mortality.
  2. Establish the safety of a single dose of azithromycin administered during the neonatal period.

This study will be conducted in several regions of Burkina Faso, including peri-urban areas of Ouagadougou and Nouna town, and rural areas that are within 4 hours' drive of a pediatric facility with capacity for performing pyloromyotomy

Read the detailed description

Child mortality in West Africa is among the highest in the world. Although child health and mortality are improving worldwide, children in the Sahel and sub-Sahel regions of West Africa have the greatest risks of mortality. Burkina Faso's current under-5 mortality rate is estimated 110 per 1,000 live births. Similar to other countries in the region, the major causes of child mortality in Burkina Faso are malaria, respiratory tract infection, and diarrhea. Malnutrition acts as a major underlying contributor to mortality. Neonatal mortality remains persistently high, with approximately 1/5th of neonatal mortality due to pneumonia, meningitis, and sepsis. Interventions that address these underlying causes may be particularly efficacious for reducing mortality.

Younger children at are at a higher risk of mortality. Approximately 2/3rd of under-5 deaths occur during the first year of life. In general, the child mortality rate decreases as age increases. While some improvement has been observed, neonatal mortality is declining at a slower rate than post-neonatal childhood mortality. Many child health interventions are designed specifically for children over 6 months of age, such as vitamin A supplementation, seasonal malaria chemoprevention, and lipid-based nutritional supplementation. Identification of strategies that are safe and effective for the youngest children will be required to address persistently high rates of neonatal and infant mortality.

The MORDOR I study demonstrated a significant reduction in all-cause child mortality following biannual mass azithromycin distribution. Across three diverse geographic locations in sub-Saharan Africa (Malawi, Niger, and Tanzania), biannual mass azithromycin distribution over a two-year period led to a 14% decrease in all-cause child mortality. In Niger, 1 in 5-6 deaths were averted. These results are qualitatively similar to those of a previous study of mass azithromycin distribution for trachoma control in Ethiopia, which found reduced odds of all-cause mortality in children in communities receiving mass azithromycin compared to control communities.

In MORDOR I, the strongest effect of azithromycin was in the youngest cohort of children. Across all three countries, the strongest effect of azithromycin was consistently in children 1-5 months of age, with an approximately 25% reduction in all-cause mortality. However, MORDOR I was not optimized to target the youngest age groups. Although children as young as 1 month were eligible, biannual distributions might not reach some children until 7 months of age. On average, children were first treated at 4 months. Given that there may be a substantial benefit to treating children at younger ages, azithromycin strategies that are designed to target younger age groups may be even more beneficial for reducing child mortality.

Here, the investigators propose a randomized controlled trial designed to evaluate the efficacy of a dose of azithromycin administered during the neonatal period for prevention of mortality within in the first 6 months of life. The investigators propose to randomize births in several geographic regions of Burkina Faso to a single dose of azithromycin or placebo between day 8 and 27 of life. This study is designed to provide evidence of the efficacy of azithromycin treatment for the youngest children.

Being tested
Azithromycin, Placebo
Keywords
childhood mortality, neonates, azithromycin, mass drug administration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AzithromycinDrug

    a single dose of Azithromycin will be administered to infants between their 8-27th days of life

  • PlaceboDrug

    a single dose of Placebo will be administered to infants between their 8-27th days of life

Study groups in NCT03682653
Study groupRoleWhat they receive
AzithromycinActive comparatora single dose of Azithromycin will be administered to infants between their 8-27th days of life
Receives: Drug: Azithromycin
PlaceboPlacebo comparatora single dose of placebo will be administered to infants between their 8-27th days of life
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6 Month Mortality - All Cause

    The primary outcome of the study was all-cause mortality rate in infants at 6 months of age.

    Measured: 6 months

Secondary outcomes (7)
  1. 12 Month Mortality - All Cause

    All-cause Mortality Rate in infants at 12 months of age

    Measured: 12 months

  2. Vital Status

    Caregivers will be asked if the child is dead or alive at 365 days of life

    Measured: 12 months

  3. Change in Weight Over Time

    Weight gain from baseline to day 180

    Measured: 6 months

  4. Change in Length Over Time

    Change in length from baseline to day 180

    Measured: 6 months

  5. Proportion of Infants Developing Infantile Hypertrophic Pyloric Stenosis

    Proportion of infants developing infantile hypertrophic pyloric stenosis between 2 to 8 weeks after treatment

    Measured: 8 weeks

  6. Adverse Events

    Caregivers will be asked if their child experienced any symptoms for pyloric stenosis since the last visit.

    Measured: 12 months

  7. Neonatal Mortality

    Mortality prior to 28 days of life

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2018
  2. Study start11 Apr 2019
  3. Primary completion1 May 2022
  4. Study completion31 Dec 2022

Resources

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 trial of azithromycin versus placebo to establish the efficacy and safety of administration of a dose of azithromycin during the neonatal period
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
21,832 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03682653
Sponsor's protocol ID
OPP1187628-B
Acronym
NAITRE
Status last verified
Jun 2023
First submitted
19 Sep 2018
Last updated
27 Jun 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data will be available as per the Bill and Melinda Gates open access policy. Individual participant data will be available that underline the reported results (texts, tables, figures, and appendices). The study protocol and statistical analysis plan will also be made available. The data will be available following publication in accordance with the BMGF guidelines.

Publications

  • Bountogo M, Sie A, Zakane A, Compaore G, Ouedraogo T, Brogdon J, Lebas E, Nyatigo F, Medvedev MM, Arnold BF, Lietman TM, Oldenburg CE; NAITRE Study Team. Infant mortality and growth failure after oral azithromycin among low birthweight and underweight neonates: A subgroup analysis of a randomized controlled trial. PLOS Glob Public Health. 2023 May 15;3(5):e0001009. doi: 10.1371/journal.pgph.0001009. eCollection 2023.

    PubMed 37186577
  • Sie A, Bountogo M, Zakane A, Compaore G, Ouedraogo T, Ouattara M, Lebas E, Brogdon J, Nyatigo F, O'Brien KS, Porco TC, Barnighausen T, Arnold BF, Lietman TM, Oldenburg CE; NAITRE Study Team. Neonatal Azithromycin Administration and Growth during Infancy: A Randomized Controlled Trial. Am J Trop Med Hyg. 2023 Mar 27;108(5):1063-1070. doi: 10.4269/ajtmh.22-0763. Print 2023 May 3.

    PubMed 36972694
  • Oldenburg CE, Sie A, Bountogo M, Zakane A, Compaore G, Ouedraogo T, Koueta F, Lebas E, Brogdon J, Nyatigo F, Doan T, Porco TC, Arnold BF, Lietman TM; NAITRE Study Team. Neonatal azithromycin administration for prevention of infant mortality. NEJM Evid. 2022 Apr;1(4):EVIDoa2100054. doi: 10.1056/EVIDoa2100054. Epub 2022 Mar 17.

    PubMed 35692260
  • Bountogo M, Sie A, Zakane A, Compaore G, Ouedraogo T, Lebas E, Brogdon J, Nyatigo F, Arnold BF, Lietman TM, Oldenburg CE. Antenatal care attendance and risk of low birthweight in Burkina Faso: a cross-sectional study. BMC Pregnancy Childbirth. 2021 Dec 13;21(1):825. doi: 10.1186/s12884-021-04310-6.

    PubMed 34903190
  • Sie A, Bountogo M, Nebie E, Ouattara M, Coulibaly B, Bagagnan C, Zabre P, Lebas E, Brogdon J, Godwin WW, Lin Y, Porco T, Doan T, Lietman TM, Oldenburg CE; NAITRE Study Group. Neonatal azithromycin administration to prevent infant mortality: study protocol for a randomised controlled trial. BMJ Open. 2019 Sep 4;9(9):e031162. doi: 10.1136/bmjopen-2019-031162.

    PubMed 31488494

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Azithromycin in people with Childhood Mortality, 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 10 inclusion and 9 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 27 Jun 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 27 Jun 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?

6 Month Mortality - All Cause (time frame: 6 months). 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 NCT03682653, which also lists 5 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 27 Jun 2023.

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