Oral Azithromycin to Prevent Stillbirths and Infant Mortality in Mali (SANTE)

Sauver Avec l'Azithromycine en Traitant Les Femmes Enceintes et Les Enfants (SANTE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Stillbirths and Infant Mortality
• Intervention / Treatment: Drug: Azithromycin to pregnant women; Drug: Azithromycin to infants; Other: Placebo to infants; Other: Placebo to pregnant women; Other: No intervention to pregnant women

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.

• Study Type: Interventional
• Enrollment (Actual): 99700
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Amanda Driscoll, PhD; Phone Number: 410-706-1226; Email: adriscoll@som.umaryland.edu
• Study Contact Backup: Name: Fleesie Hubbard, MS; Phone Number: 410-706-0431; Email: fhubbard@som.umaryland.edu

Study Locations

• Mali
  • Bamako, Mali
    • Centre pour le Developpement des Vaccins - Mali

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azithromycin to pregnant women and azithromycin to infants; 2 gram oral dose of Azithromycin to pregnant women at their 2nd and 3rd trimester antenatal care visits and during delivery, plus 20 mg/kg to 1 gram oral dose of azithromycin to infants at 6 and 14 week Expanded Programme on Immunization (EPI) visits	Drug: Azithromycin to pregnant women; Azithromycin to pregnant women at antenatal care visits and during delivery; Drug: Azithromycin to infants; Azithromycin to infants at 6 and 14 week EPI visits
Experimental: Azithromycin to pregnant women and placebo to infants; 2 gram oral dose of Azithromycin to pregnant women at their 2nd and 3rd trimester antenatal care visits and during delivery, plus oral placebo to infants at 6 and 14 week EPI visits	Drug: Azithromycin to pregnant women; Azithromycin to pregnant women at antenatal care visits and during delivery; Other: Placebo to infants; Placebo to infants at 6 and 14 week EPI visits
Experimental: Placebo to pregnant women and azithromycin to infants; Oral placebo to pregnant women at their 2nd and 3rd trimester antenatal care visits and during delivery, plus 20 mg/kg to 1 gram oral dose of azithromycin to infants at 6 and 14 week EPI visits	Drug: Azithromycin to infants; Azithromycin to infants at 6 and 14 week EPI visits; Other: Placebo to pregnant women; Placebo to pregnant women at antenatal care visits and during delivery
Placebo Comparator: Placebo to pregnant women and placebo to infants; Placebo to pregnant women at their 2nd and 3rd trimester antenatal care visits and during delivery, plus oral placebo to infants at 6 and 14 week EPI visits	Other: Placebo to infants; Placebo to infants at 6 and 14 week EPI visits; Other: Placebo to pregnant women; Placebo to pregnant women at antenatal care visits and during delivery
Experimental: No intervention to pregnant women and azithromycin to infants; No intervention to pregnant women and 20 mg/kg to 1 gram oral dose of azithromycin to infants at 6 and 14 week EPI visits	Drug: Azithromycin to infants; Azithromycin to infants at 6 and 14 week EPI visits; Other: No intervention to pregnant women; No intervention to pregnant women
Placebo Comparator: No intervention to pregnant women and Placebo to infants; No intervention to pregnant women and placebo to infants at 6 and 14 week EPI visits	Other: Placebo to infants; Placebo to infants at 6 and 14 week EPI visits; Other: No intervention to pregnant women; No intervention to pregnant women

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of stillbirths and infant mortality through 6-12 months of age	Delivery outcomes assessed at intrapartum study visit and infant vital status assessed at 6 and 12 month study visits.	6 to 12 months
Rate of infant mortality between 6 weeks and 12 months of age	Infant vital status will be assessed at 6 and 12 month study visits.	6 weeks to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gestational age at birth	Gestational age will be estimated at enrollment and at delivery.	3-6 months
Birth weight	Birth weight will be measured.	3-6 months
The incremental cost-effectiveness ratio of adding azithromycin to standard of care in Mali	Costs associated with the delivery of azithromycin will be measured and the cost-effectiveness ratio will be estimated using efficacy data from the trial.	6 to 18 months

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: Bill and Melinda Gates Foundation
• Investigators: Principal Investigator: Karen L Kotloff, MD, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): September 24, 2020
• Primary Completion (Actual): August 28, 2023
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Death; Fetal Death; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Infant Death; Stillbirth; Anti-Infective Agents; Anti-Bacterial Agents; Azithromycin
• Other Study ID Numbers: HP-00084242

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes