Oral azithromycin use during childbirth to prevent severe maternal infection among Nigerian women giving birth vaginally
| ISRCTN | ISRCTN16415327 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16415327 |
| Secondary identifying numbers | INV-056490 |
- Submission date
- 22/06/2024
- Registration date
- 03/07/2024
- Last edited
- 02/08/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
Background and study aims
Maternal sepsis is a severe infection that occurs during or after childbirth and is a significant cause of maternal deaths worldwide, particularly in Nigeria. This study aims to investigate whether giving a single 2 g dose of azithromycin, an antibiotic medication, to women during labour can reduce the risk of sepsis and related infections and its complications. This study will also evaluate how best to implement this intervention in the Nigerian healthcare system.
Who can participate?
The study will involve pregnant women who plan to give birth vaginally. There are no specific age restrictions mentioned, but all participants will be women in labour at the selected health facilities. Health workers involved in the implementation aspect of the study will also participate in study.
What does the study involve?
The study will be conducted in 60 sites in Nigeria. The health facilities will be randomly assigned to either the intervention or control group for both the clinical trial and implementation study. The study will compare two groups of participants:
For the clinical study,
Intervention group: Women will receive a single 2-g oral dose of azithromycin during labour.
Control group: Women will receive the usual care without azithromycin.
The study participants will be scheduled for follow-up visits at 3 days, 2 weeks, 4 weeks, and 6 weeks after childbirth to assess for any symptom or sign of maternal infection and/or sepsis.
The study will also collect data on the cost-effectiveness of the intervention.
For the implementation study,
Intervention group: Implementation strategies will be generated through Plan, Do, Study, Act (PDSA) cycles by the healthcare personnel (bottom-up approaches).
Control group: One-off training workshops and distribution of guidelines for administering azithromycin (top-down approach).
What are the possible benefits and risks of participating?
Participants in the intervention group may benefit from a reduced risk of sepsis and related complications. However, as with any antibiotic treatment, there may be potential side effects such as nausea, diarrhoea, or allergic reactions. The control group will continue to receive the standard care currently provided at the selected health facility.
Where is the study run from?
The College of Medicine of the University of Lagos (Nigeria)
When is the study starting and how long is it expected to run for?
September 2023 to August 2026
Who is funding the study?
Bill & Melinda Gates Foundation (USA)
Who is the main contact?
Prof. Bosede B. Afolabi, bbafolabi@unilag.edu.ng
Contact information
Public, Scientific, Principal Investigator
Department of Obstetrics and Gynaecology
College of Medicine
University of Lagos
Ishaga Road
Idi-Araba
Lagos
100254
Nigeria
 ORCID ID |
0000-0002-7511-7567 |
|---|---|
| Phone | +234 (0)8023154064 |
| bbafolabi@unilag.edu.ng |
Department of Obstetrics and Gynaecology
College of Medicine
University of Lagos
Lagos
-
Nigeria
| Phone | +234 (0)8033358021 |
|---|---|
| makwe285@yahoo.com |
Centre for Clinical Trials
Research and Implementation Science
College of Medicine
University of Lagos
Lagos
-
Nigeria
| Phone | +234 (0)8022089798 |
|---|---|
| teniola.lawanson@cctris.org |
Study information
| Study design | Hybrid type-2 effectiveness-implementation national multicenter parallel-group open-label cluster randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention, Treatment, Safety, Efficacy |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | Azithromycin use in labour to prevent maternal sepsis among pregnant women undergoing vaginal birth in Nigeria (AZIN-V): a cluster-randomised hybrid type-2 effectiveness implementation trial |
| Study acronym | AZIN-V |
| Study objectives | Azithromycin use in labour reduces maternal sepsis among pregnant women undergoing vaginal birth in Nigerian when compared to usual care. |
| Ethics approval(s) |
Approved 30/11/2023, Lagos University Teaching Hospital Health Research Ethics Committee (Room 107, 1st Floor, LUTH Administrative Block, Lagos University Teaching Hospital (LUTH) Idi-Araba, Lagos, 100254, Nigeria; +234 (0)8023305199; oysofola@yahoo.com), ref: ADM/DSCST/HREC/APP/6325 |
| Health condition(s) or problem(s) studied | Prevention of maternal sepsis among pregnant women undergoing vaginal birth |
| Intervention | 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 control sites, and the sites will be strongly counselled to ensure that azithromycin is not made available for use. All participants (intervention and control sites) will be followed up until discharge and surveillance maintained (in-person), with visits at 3 days, then 2, 4 and 6 weeks, after delivery. Implementation study: Interventional group: The PDSA cycle is the implementation strategy to improve the adoption and implementation of azithromycin during vaginal birth in the intervention healthcare facilities. For the implementation study, the researchers will establish a multidisciplinary team comprising obstetricians and gynaecologists, nurses, midwives, pharmacists, administrators (including data managers or clerks), participant representatives, and any other stakeholders that may be conscripted as necessary at the health facility level to ensure the integration of equity-informed methodologies into all research strategies of this study, ownership, and sustainability. The team will oversee the generation and testing of strategies and record and review data to determine if strategies lead to improvement and if improvements are being sustained. Control group: In the control sites, the usual strategy of one-off training workshops and distributing guidelines for administering the new treatment will be instituted. Afterwards, the new intervention is introduced. This approach is usually top-down with minimal involvement of the SHP, who will deliver the intervention to the pregnant women. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Azithromycin |
| Primary outcome measure | Primary outcome measures for the clinical trial: 1. Incidence of maternal sepsis is measured using clinical and laboratory parameters at four timepoints after childbirth: day 3, 2 weeks, 4 weeks, and 6 weeks post-delivery. 2. Cost-effectiveness is measured using Incremental Cost-Effectiveness Ratio (ICER) at baseline and 6 weeks post-delivery: additional cost per unit of health gain with azithromycin compared to the usual care for individual participants as a component of the sepsis prevention protocol in healthcare facilities. Primary outcome measure for the implementation study: 1. Fidelity is measured using health facility records and observation checklist during implementation and endline. |
| Secondary outcome measures | Secondary outcome measures for the clinical trial: 1. Incidence of culture-confirmed maternal sepsis is measured using microbiological positive culture results at timepoints within 6 weeks of childbirth 2. Number of new prescriptions of antibiotics for a specific maternal infection (including bacterial vaginosis, chorioamnionitis, endometritis, abdominal or pelvic abscess, mastitis or breast abscess, pneumonia, or pyelonephritis or acute cystitis) measured using medical records and questionnaire at 6 weeks of childbirth 3. Incidence of neonatal sepsis within 28 days of birth is measured using clinical and laboratory parameters at time points within 28 days of birth 4. Incidence of stillbirth measured using questionnaire at baseline 5. Incidence of neonatal death measured using questionnaire at day 29 of birth 6. Duration of initial hospital stay for neonate, defined as the time of delivery until the time of hospital discharge, measured using medical records and questionnaire at day 29 of birth 7. Incidence of neonatal readmission is measured using medical records and questionnaire at day 29 of birth 8. Duration of hospital stay for mother is measured using medical records and questionnaire at 6 weeks after childbirth 9. Incidence of maternal readmission is measured using medical records and questionnaire at 6 weeks after childbirth 10. Incidence of adverse drug events (fainting or dizziness, nausea, vomiting, diarrhoea, and dyspepsia) and other reported side effects measured using medical records and questionnaire at 2 weeks after childbirth 11. Incidence of secondary post-partum haemorrhage, defined as excessive bleeding requiring surgical intervention or blood transfusion from 24 hours after delivery till 6 weeks postpartum, measured using medical records and questionnaire at 6 weeks after childbirth Secondary outcome measures for the implementation study: 1. Reach is measured using health facility records and observation checklist during implementation and endline 2. Adoption is measured using the Organizational Readiness for Implementing Change (ORIC) tool, key informant interviews (KIIs), and focused group discussions (FGDs) at baseline and endline 3. Feasibility is measured using in-depth interviews (IDIs) and focused group discussions (FGDs) at baseline and endline 4. Acceptability is measured using KIIs and FGDs at baseline and endline 5. Sustainability acceptability is measured using KIIs at endline |
| Overall study start date | 30/09/2023 |
| Completion date | 30/08/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 50 Years |
| Sex | Female |
| Target number of participants | 5040 |
| 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 |
| 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 |
| Date of first enrolment | 30/06/2024 |
| Date of final enrolment | 30/03/2026 |
Locations
Countries of recruitment
- Nigeria
Study participating centres
Lagos
100254
Nigeria
Ishaga Road, Idi-Araba Surulere
Lagos
100254
Nigeria
Sponsor information
University/education
College of Medicine
Ishaga Road, Idi-Araba Surulere
Lagos
100254
Nigeria
| Phone | +234 (0)8023356454 |
|---|---|
| oobafemimoses@unilag.edu.ng | |
| Website | https://cmul.unilag.edu.ng/ |
"ROR" |
https://ror.org/05rk03822 |
Funders
Funder type
Charity
Government organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Bill & Melinda Gates Foundation, Gates Foundation, BMGF, B&MGF, GF
- Location
- United States of America
Results and Publications
| Intention to publish date | 30/08/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be available on request from Prof. Bosede B. Afolabi (bbafolabi@unilag.edu.ng) |
Editorial Notes
02/08/2024: Contact details updated.
03/07/2024: Study's existence confirmed by the Lagos University Teaching Hospital Health Research Ethics Committee.
