Pre-delivery Administration of Azithromycin to Prevent Neonatal Sepsis & Death
Status:
Completed
Trial end date:
2021-05-31
Target enrollment:
Participant gender:
Summary
Though maternal and neonatal health are high priority areas for international development,
maternal and neonatal mortality remain unacceptably high. Worldwide there are 1 million
maternal and 4 million neonatal deaths every year and half of them occur in sub-Saharan
Africa.
Post-partum and neonatal severe bacterial infections, namely sepsis, are leading causes of
maternal and neonatal deaths in sub-Saharan Africa. Newborns can be infected during labour -
when passing through the birth canal - and also during the first days/weeks of life, as a
consequence of the close physical contact with the mother, when the latter carriers bacteria.
As the mother is an important source of bacterial transmission to the newborn, treating
mothers with antibiotics during labour should decrease their bacterial carriage and therefore
lower transmission to the newborn. As carriage is a necessary step towards severe disease,
this intervention should in turn result in the lower occurrence of severe bacterial disease
and mortality during the neonatal period.
In many high-income countries, pregnant women are screened during pregnancy for vaginal
carriage of Group B Streptococcus, the bacteria responsible for the vast majority of neonatal
sepsis in the developed world. If women are carriers, they are treated with intravenous
antibiotics during labour to decrease the risk of severe disease to their off-spring.
Although this intervention has been successful in developed countries, infrastructure and
resource limitations in regions like sub-Saharan Africa prevent both screening and use of
intravenous antibiotics. Also, in Africa several bacterial pathogens are responsible for
neonatal sepsis and the antibiotics needed in the continent should cover a wider number of
bacteria; and ideally cover also bacteria responsible for severe post-partum disease in the
mother.
We will conduct a large trial in West Africa, The Gambia and Burkina Faso, with the main
objective of determining if a single dose of an oral antibiotic given to women during labour
decreases newborn mortality. The trial will also assess the effect of the antibiotic on
lowering newborns and maternal hospitalization during the first week's post-partum. We have
selected an antibiotic (azithromycin) that in sub-Saharan Africa has already been used for
elimination of other prevalent diseases such as trachoma. This antibiotic is safe, requires a
single oral administration, has no special storage requirements and has the potential to
eliminate most of the bacteria commonly causing severe disease in newborns and post-partum
women in the continent. Very important this antibiotic is not widely used in clinical care in
the continent, and therefore, any temporal increase of resistance induced by the intervention
should not have implications on current treatment guidelines.
Before going to the large trial proposed here (12,000 women to be recruited), we have
generated robust preliminary data on the effect of the intervention in a proof-of-concept
trial conducted in The Gambia (829 women and their offspring recruited). We found that in
fact, babies born from mothers who had taken this antibiotic during labour were less likely
to carry bacteria that can potentially cause severe disease. These babies were also three
times less likely to have bacterial skin infections or umbilical infections, both highly
common among African newborns. Besides, fever or mastitis (again both very common in the
region) during the post-partum period were four times lower among mothers who had taken the
antibiotic during labour. Such trial confirmed our hypothesis of impact on bacterial
transmission but it was too small to assess the effect of the antibiotic on mortality and
hospitalizations. The preliminary trial also showed that women from the azithromycin group
were less likely to need antibiotics for treatment infections during the puerperal period,
decreasing then the pressure on the scarcity of antibiotics available in the continent.
The advantages of our approach are its simplicity, low cost and the possibility of protecting
both mothers and babies with the same intervention.
Phase:
Phase 3
Details
Lead Sponsor:
London School of Hygiene and Tropical Medicine Medical Research Council Unit, The Gambia