Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03682653 |
| Other study ID # |
OPP1187628-B |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
April 11, 2019 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
June 2023 |
| Source |
University of California, San Francisco |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
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
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.
