Prevention of Invasive Group B Streptococcus Disease in Young Infants: a Pathway for the Evaluation & Licensure of an Investigational Maternal GBS Vaccine (Work Package 2)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 3,423
- Locations
- 1
- Primary Endpoint
- Maternal gestational diabetes mellitus
Study Overview
Brief Summary
Maternal immunisation is an evolving field that deserves special attention given its potential to have a significant positive impact on the health of women and children globally, and the potential safety and risk considerations associated with research in this population.
The goal of maternal immunisation is to boost maternal levels of specific antibodies to provide the newborn and young infant with sufficient immunity at birth, through trans placental transfer in-utero, to protect them through the period of increased vulnerability. Protection should be adequate to last until they are able to respond to their own active immunisations or infectious challenges. The success of the maternal neonatal tetanus immunisation program demonstrates the utility of this approach. Several other vaccines are recommended in pregnancy, including influenza and pneumococcal vaccines. Promising new vaccines for group B streptococcus (GBS) , respiratory syncytial virus (RSV) and cytomegalovirus are under development. They are targeted for use in pregnant women in high-, middle-, and low-income countries. However, these vaccines are likely to be of most benefit in LMICs that have high rates of vaccine preventable diseases.
The second work-package (WP2) of the PREPARE portfolio will describe the baseline maternal and neonatal outcomes using anonymised data collected using the routine Kawempe electronic medical records (EMR) system.
Furthermore, comprehensive data on pregnancy, neonatal and infant outcome will also be collected in a prospective cohort of women enrolled in the first and second trimesters while attending antenatal care at Kawempe Hospital with follow-up of the mother-infant pair(s) up until at least 14 weeks postpartum to establish longer term outcomes. Standardised case definitions will be used to classify the outcomes.
Detailed Description
Maternal Immunisation research in LMICs
Maternal immunisation is an evolving field that deserves special attention given its potential to have a significant positive impact on the health of women and children globally, and the potential safety and risk considerations associated with research in this population.
Prior to undertaking any maternal vaccine study, it is vital that the background rates of pregnancy and neonatal outcomes are clearly documented as these vary by setting, so that safety signals during vaccine trials can be correctly assessed . Given the important contribution that maternal immunisations could make to reducing maternal and neonatal morbidity, efforts are underway to standardise case definitions used to classify adverse events in maternal vaccine trials. Historically, this has not been the case, limiting comparability between countries and pre and post-licensure. In 2014, in response to a call from the World Health Organisation (WHO) and with funding from the Bill & Melinda Gates Foundation, the GAIA (Global Alignment on Immunisation Safety Assessment in pregnancy) consortium was formed, with the goal of developing a harmonised, globally concerted approach to actively monitor the safety of clinical trials, vaccines and immunization programs in pregnancy. The group have developed 21 standardised case definitions for the classification of adverse obstetric and neonatal events including the need to follow up vaccinated women for 6 months and infants for one year following vaccination.
Study Setting Uganda has a long history of conducting prevention of mother to child HIV transmission (PMTCT) trials as well as vaccine trials for Ebola and Human Immunodeficiency Virus 9. The established National Drug Authority (NDA) and National Immunisation Technical Advisory Group (NITAG) provide pharmacovigilance capacity and an effective platform for monitoring drug and vaccine safety. Makerere University John Hopkins University Research Collaboration (MUJHU) has led multiple PMTCT and HIV therapeutic trials 10. This collaboration with St George's University, who are leaders in immunisation research, presents a unique opportunity to develop a maternal vaccination platform for future trials in Uganda.
Funding has been provided from the European Developing Countries Clinical Trials Partnership (EDCTP) to develop a maternal vaccine trial platform at Kawempe National Referral Hospital. It is anticipated that a tetanus, diptheria and acellular pertussis (Tdap) study will be conducted in 2020 followed by two GBS vaccine trials.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 14 Years to — (Child, Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Maternal gestational diabetes mellitus
Time Frame: 24 months
To describe proportion (%) of women diagnosed with gestational diabetes mellitus in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Maternal deaths in a prospective cohort.
Time Frame: 24 months
To describe proportion (%) of maternal deaths in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Fetal growth restriction
Time Frame: 24 months
To describe proportion (%) of pregnancies diagnosed with fetal growth restriction in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Maternal, neonatal and infant mortality - Electronic Medical Records.
Time Frame: 24 months
To describe the maternal and neonatal mortality (%) using hospital electronic medical records (EMR).
Hypertensive disorders
Time Frame: 24 months
To describe proportion (%) of women that experience hypertensive disorders of pregnancy in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Haemorrhage
Time Frame: 24 months
To describe proportion (%) of women that experience antepartum or postpartum haemorrhage in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Spontaneous abortions & ectopic pregnancy
Time Frame: 24 months
To describe proportion (%) of women that experience spontaneous abortions and ectopic pregnancies in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Birth outcomes (low-birthweight, stillbirths, prematurity)
Time Frame: 24 months
To describe proportion (%) of births that are low-birthweight, premature or stillborn in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Infant Outcomes
Time Frame: 24 months
To describe proportion (%) of liveborn babies that die in infancy in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Chorioamnionitis & endometritis
Time Frame: 24 months
To describe proportion (%) of women that experience chorioamnionitis, endometritis or infection following incomplete abortion in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Fetal distress and dysfunctional labor
Time Frame: 24 months
To describe proportion (%) of women that experience fetal distress or dysfunctional labor in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Neonatal outcomes
Time Frame: 24 months
To describe proportion (%) of liveborn babies that are diagnosed with neonatal encephalopathy, neonatal infections, respiratory distress, seizures or die in the neonatal period in a prospective cohort of 4000 mother infant dyads using standardised Global Alignment of Immunisation Safety Assessment in Pregnancy (GAIA) definitions.
Secondary Outcomes
- Maternal, obstetric, neonatal and infant outcomes - Electronic Medical Records(24 months)