Clinical trial NCT03909737: Oral Azithromycin to Prevent Stillbirths and Infant Mortality in Mali
Official title: Sauver Avec l'Azithromycine en Traitant Les Femmes Enceintes et Les Enfants (SANTE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Stillbirths and Infant Mortality
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2019-04-10
Enrollment: 99700
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This study will enroll three study cohorts: (1) a rural cohort of pregnant mother-infant pairs based in the southern region of Sikasso where infant mortality rates are higher than the national average (2) a rural cohort of only infants enrolled from the same communities as the mother-infant pairs, and (3) an urban cohort of pregnant mother-infant pairs based in Bamako. Cohort 1 will use a 2x2 factorial design. The pregnant women will be randomized to receive either oral azithromycin or placebo, and their infants, once born, will be separately randomized to receive either oral azithromycin or placebo. Cohorts 2 and 3 will use a parallel design. In Cohort 2, infants will be randomized to either azithromycin or placebo. In Cohort 3, mother-infant pairs will be randomized in tandem to either azithromycin or placebo.
Primary purpose: PREVENTION

Brief summary: The double blind randomized controlled trial will assess the efficacy of oral azithromycin administered to pregnant women and/or infants during routine care in preventing stillbirths and mortality through 6-12 months of age in Mali, West Africa, where rates of infant and under five mortality are among the highest in the world.

Detailed description: This trial will assess the efficacy of oral azithromycin given during routine health care visits in preventing stillbirths and mortality through 6-12 months of age in Mali, West Africa, where rates of infant and under five mortality are among the highest in the world. Using an individually randomized placebo-controlled double-masked trial design, pregnant women will receive a single dose of oral azithromycin or placebo at their second and/or third trimester antenatal care visits and during labor, and to infants at their DPT-1 and DPT-3 vaccination visits, which occur at approximately 6 and 14 weeks of age, respectively. The two co-primary outcomes are (1A) a composite outcome of stillbirths and mortality through 6-12 months of age and (1B) mortality between 6 weeks and 6-12 months of age. The study sample size is powered to detect a 20% relative reduction in both of the two co-primary outcomes. The study is designed to inform policymakers regarding the effectiveness of azithromycin for the prevention of stillbirth and infant mortality in both urban and rural parts of the country when administered during routine antenatal and intrapartum care and infant immunization visits. To achieve this aim, three cohorts will be enrolled: a mother-infant cohort in a rural part of the country with infant mortality rates that are higher than the national average, a supplemental infant-only cohort enrolled form the same rural communities, and third urban mother-infant cohort residing in Bamako, Mali's capital. Sub studies designed to elucidate the protective mechanisms of azithromycin treatment will be embedded within the larger study and will be added in the future.

Eligibility criteria: Inclusion Criteria:

Pregnant women:

1. Participant is attending an ANC visit between 13 and 37 weeks gestation, with gestational age estimated using fundal height measurements and/or maternal report of quickening, at a participating health facility.
2. Participant is able to understand and comply with planned study procedures.
3. Participant has provided informed consent prior to initiation of any study procedures.
4. Participant intends to reside in the study area until her newborn infant is at least 12 months old.

Infants:

Enrollment of pregnant women and their unborn infants will happen simultaneously. Infants attending routine immunization visits at eligible health facilities whose mothers were not enrolled in the study will be eligible for enrollment in the supplemental infant cohort within the rural study cohort with the following inclusion criteria:

1. Infant is \<12 mo attending a DTP-1 routine vaccination visit at a participating health facility.
2. Parent or guardian is able to understand and comply with planned study procedures.
3. Parent or guardian has provided informed consent prior to initiation of any study procedures.
4. Parent or guardian intends to reside in the study area until participant is at least 12 months old.

Exclusion Criteria:

1. Allergy to macrolides or azalides.
2. Any condition that, in the opinion of the investigator, might compromise the well-being of the participant or compliance with study procedures.
3. Medical treatment that requires administration of azithromycin (this can be a temporary exclusion if the drug is later discontinued).

Primary outcomes:
measure: Rate of stillbirths and infant mortality through 6-12 months of age
timeFrame: 6 to 12 months
measure: Rate of infant mortality between 6 weeks and 12 months of age
timeFrame: 6 weeks to 12 months
Secondary outcomes:
measure: Gestational age at birth
timeFrame: 3-6 months
measure: Birth weight
timeFrame: 3-6 months
measure: The incremental cost-effectiveness ratio of adding azithromycin to standard of care in Mali
timeFrame: 6 to 18 months
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Centre pour le Developpement des Vaccins - Mali
Study officials:
affiliation: University of Maryland, Baltimore
name: Karen L Kotloff, MD
role: PRINCIPAL_INVESTIGATOR
References: