Feasibility study for the development of a sero-correlate of protection against invasive Group B Streptococcus disease (the iGBS study)

Plain English Summary

Background and study aims
Group B Streptococcus (GBS) is a bacterium (bug) that causes infection in young infants in all regions of the world. Worldwide in 2015 it was estimated that there were at least 319,000 infants under 3 months of age with GBS disease, resulting in 90,000 deaths and at least 10,000 children with long-term disabilities. Babies mostly acquire the GBS bacteria from their mothers around the time of birth and around 20% of all pregnant women carry GBS in their bowel and vagina. The global burden of GBS is therefore high and the options for prevention are currently limited. An effective vaccine that could be given to pregnant women has the greatest potential to benefit mothers and babies worldwide and such vaccines are now being tested in clinical trials, including in pregnant women. To license a new vaccine so that it can be recommended for routine use usually requires evidence that the vaccine is safe and effective in preventing the disease. This usually means undertaking a large trial in which the new vaccine is given to half of the subjects, who are then compared to the other half who did not receive the new vaccine. Such trials are expensive and time-consuming to perform. Another way of licensing a new vaccine is to show that when it is given to relevant groups of people it is able to produce levels of immunity (usually measured as antibodies) in their blood that are known to result in protection. Such levels are called serocorrelates (because they “correlate” with protection). Although there is considerable evidence that high levels of antibody against GBS in pregnant women do correlate with protection against GBS disease in their babies, the precise level (the serocorrelate) is not currently known. Although GBS is the most common cause of serious early infections in UK babies it is still relatively rare overall, so around 150,000 babies will need to be followed in order to find at least 150 babies with GBS disease, which is around the number needed to establish the serocorrelates of protection. The aim of this smaller (feasibility) study of around 4000 women is to assess the recruitment and test the methods. If this feasibility study works well this will lead to a larger study to address the question of how much antibody is needed to protect against invasive infant GBS disease.

Who can participate?
Pregnant women aged 18 and over who are delivering at one of the selected hospitals

What does the study involve?
A small sample of blood is collected from pregnant women and/or from the cord of their newborn babies at delivery and stored in the laboratory. With the cooperation of paediatricians and microbiologists the researchers are alerted if any of the babies develop GBS disease over the next 3 months. For those who do, the level in their blood samples at birth is then compared with that of other babies who did not develop GBS disease. Because many babies acquire GBS from their mothers at birth a smaller number of the mothers have a swab taken to see if they are carrying GBS around the time of birth.

What are the possible benefits and risks of participating?
The antibody tests will help in the development and licensure of GBS vaccines for pregnant women. It is hoped that the results of this study will help to stop babies from becoming sick with GBS disease in the future. A blood sample can cause anxiety for some people and is associated with mild, temporary discomfort. There is a small risk of fainting, bruising and infection. All blood sampling is performed by trained members of the study team. If required, a blood sample may be needed from the baby at 1-3 months (less than a teaspoon full). This can cause discomfort but common distraction techniques, such as breastfeeding, can be used to minimize this. In the unlikely case of a stillbirth, participants are still asked if they are happy to consent for a blood test. This can provide useful information as GBS is a cause of stillbirths.

Where is the study run from?
1. St George’s University Hospitals NHS Foundation Trust (UK)
2. Kingston Hospitals NHS Trust (UK)
3. Croydon University Hospitals NHS Trust (UK)
4. East Surrey Hospitals NHS Trust (UK)
5. Poole Hospital NHS Trust (UK)

When is the study starting and how long is it expected to run for?
June 2018 to August 2020

Who is funding the study?
NIHR Health Technology Assessment Programme (UK)

Who is the main contact?
Prof. Paul Heath

Study website

Contact information

Prof Paul Heath
Scientific

St George's University of London
Cranmer Terrace
Paediatric Infectious Diseases Research Group
Jenner Wing, Level 2
London
SW17 0RE
United Kingdom

ORCID ID	0000-0002-7540-7433

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

St George's University Hospitals NHS Foundation Trust
Hospital/treatment centre

St George's Joint Research Enterprise Services
Hunter Wing, Ground Floor
Cranmer Terrace
London
SW17 0QT
England
United Kingdom

Phone	+44 (0)208 725 0794
Email	researchgovernance@sgul.ac.uk
Website	https://www.stgeorges.nhs.uk/
"ROR"	https://ror.org/039zedc16

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN49326091_Protocol_V9.0_06Oct2020.pdf

Editorial Notes

19/08/2022: Protocol file uploaded.
15/04/2020: The overall trial end date was changed from 01/03/2020 to 31/08/2020.
22/01/2020: The overall trial end date was changed from 01/02/2019 to 01/03/2020.
20/12/2019: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
07/11/2018: The following changes were made:
1. The recruitment end date was changed from 02/10/2018 to 31/12/2018.
2. The overall trial end date was changed from 31/12/2018 to 01/02/2019.
3. The intention to publish date was changed from 30/04/2019 to 01/06/2019.