Prevention of Bacterial Infections in Newborn

Study Overview
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Brief Summary
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The last decade has witnessed an important reduction of the mortality in children under 5 years but such reduction has not impacted in neonates. Mortality in neonates contributes 40% of all deaths occurring in children below 5 years of age. Severe bacterial disease is among the leading causes of neonatal deaths. Bacterial disease follows bacterial infection. Individuals can be infected without developing disease (carriage stage) but infection is needed to subsequently develop disease. In sub-Saharan Africa, bacterial carriage (i.e. in the birth canal and/or nasopharyngeal tract) is very common in all age groups, with the consequence that occurrence of bacterial disease is one of the highest in the world. Newborns can be infected during labour - when passing through the birth canal - and during the first days/weeks of life, as a consequence of the close physical contact with the mother, if the latter carries bacteria in the nasopharyngeal tract. If the mother is an important source of bacterial infection to the newborn, treating mothers with a powerful antibiotic during labour should decrease bacterial carriage and therefore diminish the risk of bacterial transmission to the newborn during the first days/weeks of life, which should in turn result in the lower occurrence of severe bacterial disease and hence lower mortality. The purpose of this trial is to evaluate the impact of a single oral dose of azithromycin given to women in labour on bacterial carriage of the newborn as well as the women during the first month after delivery. The investigators have selected an antibiotic (azithromycin) that in sub-Saharan Africa has already shown both a strong impact on bacterial nasopharyngeal carriage and on all-cause mortality when administered to everybody in a community (mass drug administration). This specific antibiotic has several advantages for being deployable as a simple intervention in rural Africa, i.e. it requires a single oral administration, it has no special storage requirements and it has the potential to eliminate many of the bacteria commonly causing severe disease in newborn. This clinical trial will be conducted in a peri-urban health facility in Western Gambia. If an impact is shown, the next step would be to conduct a larger study aiming at establishing if the intervention, implemented at a lower level of care (most African women deliver at home assisted by traditional birth assistants), decreases the occurrence of neonatal bacterial disease

Official Title
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Prevention of Bacterial Infections in the Newborn by Pre-delivery Administration of Azithromycin (AZI): a Placebo-controlled Randomized Trial

Conditions
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Neonatal Infection

Intervention / Treatment
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* Drug: Azithromycin and Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women (aged 18 to 45 years) in labour attending a health centre in western Gambia for delivery Exclusion Criteria: Known HIV infection. Any chronic or acute conditions of the women that might interfere with the study as judged by the research clinician. Planned travelling out of the catchment area during the following 2 months (follow-up period) Planned caesarean section Known required referral Known multiple pregnancy Known severe congenital malformation Intrauterine death confirmed before randomization Known allergy to macrolides Consumption of antibiotic within the week before randomisation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>830 women will be recruited into the study and randomised in a ratio of 1:1 per study arm to receive either Azithromycin or placebo. A single dose of Azithromycin 2g or Placebo will be given orally to pregnant women in labour. | Drug: Azithromycin and Placebo<br>* A single oral dose of 2g of Azithromycin will be given to the women in labour<br>|
| Experimental: Azithromycin<br>830 women will be recruited into the study and randomised in a ratio of 1:1 per study arm to receive either Azithromycin or placebo. A single dose of Azithromycin 2g or Placebo will be given orally to pregnant women in labour. | Drug: Azithromycin and Placebo<br>* A single oral dose of 2g of Azithromycin will be given to the women in labour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the prevalence of nasopharyngeal carriage of the newborn of any of the following bacteria: 1) Group B Streptococci (GBS) , 2) S.pneumoniae and 3) S.aureus | The primary outcome is the prevalence of nasopharyngeal carriage of the newborn at the age of six days for any of the following bacteria: 1) Group B Streptococci, 2) S.pneumoniae and 3) S.aureus. | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal bacterial Group B Streptococci(GBS), S.pneumoniae and S.aureus) carriage at day six post-delivery. Vaginal bacterial (GBS, S.pneumoniae and S.aureus) carriage at day 8-10 post-delivery | The secondary outcomes are the prevalence of: - Newborn's nasopharyngeal bacterial Group B Streptococci (GBS), S.pneumoniae and S.aureus) carriage at any other scheduled visit. Bacterial isolates Group B Streptococci (GBS), S.pneumoniae and S.aureus), both from the newborn and the mother, non-susceptible to macrolides, from different study samples and time-points. Bacterial Group B Streptococci (GBS), S.pneumoniae and S.aureus) carriage in the breast milk at any scheduled visit. Purulent conjunctivitis within the first 4 weeks of life. Purulent Chlamydial conjunctivitis. AZI levels in breast milk on day 3 and 6 post-delivery. | 6-13 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prevention, bacterial infection, neonates, women in labour, Azithromycin