Azithromycin use in labour to prevent maternal sepsis among pregnant women undergoing vaginal birth in Nigeria (AZIN-V): a hybrid type-2 effectiveness implementation trial
Prevention of maternal sepsis among pregnant women undergoing vaginal birth
The AZIN-V study will be a cluster-randomized controlled trial with parallel assignment using a 1:1 allocation ratio for both the clinical trial and implementation study. A total of 60 study sites will be selected and randomised based on a minimisation algorithm, with factors to be considered including state (geographical location of the study site), level of care provided at the selected health facility (primary, secondary, or tertiary), and historical data on the use empirical use of postpartum antibiotics. Randomisation may occur in several waves, with at least 8 participating study sites per randomisation wave, based on the timing of signing the site-level agreement and commitment to stay in study group allocation. Study sites will be informed of their random allocation before any participant eligibility assessments. This randomisation approach ensures that prognostic factors are evenly distributed between the intervention and control groups, thereby enhancing the validity and reliability of the study results. For the clinical trial, a total of 48 study sites will be randomly assigned in a 1:1 ratio, with 24 sites randomised to intrapartum administration of a single 2-g oral dose of azithromycin (intervention group), and 24 study sites randomised to usual care without azithromycin (control group). For the implementation study, a total of 12 study sites will be randomised using a 1:1 ratio, with 6 sites randomised to adaptive Plan, Do, Study, Act (PDSA) cycles (bottom-up approach), and 6 sites randomised to the usual top-down approach. Clinical trial: Participants in intervention sites: A single 2 g oral dose of azithromycin will be administered to all eligible women in active labour who give consent in the randomised intervention sites. Participants in control sites: Eligible women recruited in control sites will receive the usual care such as handwashing, use of hand gloves, antisepsis and aseptic techniques. Azithromycin will not be provided at the cont
Current key inclusion criteria as of 26/11/2025: 1. Pregnant women with a live or stillborn singleton or twin pregnancy of at least 24+0 weeks gestation in the active phase of the first stage of labour (cervical dilatation of 4cm or more) or early (non-pushing) phase of the second stage of labour. 2. Pregnant women admitted in labour to the selected health facilities following spontaneous or induced labour with a planned vaginal birth. _____ Previous key inclusion criteria: 1. Pregnant women with singleton or multiple pregnancies of at least 24+0 weeks GA in labour including those in the first stage with cervical dilatation of ≥7 cm or in the second stage of labour 2. Admitted in labour to the participating health facilities for spontaneous or induced vaginal birth 3. Women presenting with stillbirth will also be eligible since they are at risk of postpartum sepsis
Current key exclusion criteria as of 26/11/2025: 1. Pregnant women of gestational age <24 weeks. 2. Pregnant women not admitted to the facility with a plan to deliver vaginally. 3. Pregnant women in threatened preterm labour and no immediate plan for birth. 4. Pregnant women with fever >38°C. 5. Pregnant women with history of use of a macrolide antibiotic in the previous three days. 6. Pregnant women with known allergy to azithromycin, its excipients, or other macrolide antibiotics. 7. Pregnant women with known history of cardiac disease (such as cardiac arrhythmia or cardiomyopathy). 8. Pregnant women with planned caesarean birth. _____ Previous key exclusion criteria: 1. Gestational age <24 weeks at screening 2. Not admitted to the facility with a plan to deliver vaginally 3. In preterm contraction and no immediate plan for delivery 4. Has fever >38°C with no other explanation 5. Has evidence of macrolide antibiotic use in the previous three days 6. Known allergy to azithromycin or its excipients or other macrolides 7. Known to have an arrhythmia or a known history of cardiomyopathy 8. Planned caesarean delivery