Title: Pre-delivery administration of azithromycin to prevent neonatal sepsis and death: a phase III double-blind randomized clinical trial
Funder: Medical Research Council

Abstract: The primary objective of the study is assess the effect of one oral dose of azithromycin (2g) given to women in labour on neonatal mortality (from birth to day 28). Exclusion criteria include: stillbirths; severe birth asphyxias (Apgar score 1-3); severe congenital malformations and; very low birth weight (<1.5Kg). In addition the trial will also evaluate the effect of the intervention on other clinical endpoints in both neonates and mothers, and on microbiological endpoints (prevalence of carriage and resistance): Secondary endpoints: (i) Neonates (from birth to 28 days of life) – to evaluate the effect of the intervention in the a. Prevalence of neonates with clinical sepsis b. Prevalence of neonates with culture-confirmed sepsis c. Prevalence of neonates hospitalised d. Prevalence of neonatal mortality among VLBW e. Prevalence of neonates with skin infection f. Prevalence of neonates with bacterial conjunctivitis g. Prevalence of neonates with umbilical infections h. Prevalence of neonates with malaria i. Prevalence of neonates taking antibiotics (ii) Infants (1,000 babies per country followed up to 1 year) – to evaluate the effect of the intervention in the a. Prevalence of all cause-mortality b. Prevalence of <-2SD Z-scores for height-for-age (HAZ), weight-for-age (WAZ), weight-for-height (WHZ), body mass index-for-age, head circumference-for-age, and MUAC for age (at 28 days, 6, 9 and 12 months). (iii) Mothers (post-partum period – up to 28 days after delivery) – to evaluate the effect of the intervention in the a. Prevalence of women with post-partum sepsis b. Prevalence of women with post-partum mastitis c. Prevalence of women with post-partum malaria d. Prevalence of women with post-partum fever e. Prevalence of women taking antibiotics during the post-partum period f. Prevalence of all cause-hospitalisation during the post-partum period g. Prevalence of all cause-mortality during the post-partum period ) (iv) Microbiological objectives (for all hospitalised newborns) – to evaluate the effect of the intervention in the a. Prevalence of S. pneumoniae and Klebsiella spp in the nasopharynx. b. Prevalence of E.Coli and Pseudomonas spp in the rectal tract. c. Prevalence of S. aureus, GBS, GAS in the oropharynx. (v) Microbiological objectives (random selection of 250 participant pairs in each country) – to evaluate the effect of the intervention in the a. Prevalence of S. pneumoniae and Klebsiella spp from nasopharyngeal swabs (NPS) collected at birth (day 0), day 6, day 28 and 4 months of age. b. Prevalence of E.Coli and Pseudomonas spp from RS collected at birth (day 0), day 6, day 28 and 4 months of age c. Prevalence of S. aureus, GBS and GAS from oropharyngeal swabs (OPS) collected at birth (day 0), day 6, day 28 and 4 months of age. d. Prevalence of S. aureus, GBS, GAS, E. Coli, Pseudomonas spp and Klebsiella spp in the breast milk samples collected at day 6, day 28 and 4 months. (vi) Qualitative research: a. Perceptions and acceptability of taking antibiotic during labour among pregnant women and the study communities. (vii) Health economics a. Costs of delivering azithromycin during labour in a health facility b. Cost of a newborn death. c. Hospitalisation treatment costs. d. Disability Adjusted Life Years prevented by the intervention.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION;INFLAMMATORY AND IMMUNE SYSTEM