Condition category
Infections and Infestations
Date applied
19/08/2019
Date assigned
23/08/2019
Last edited
27/08/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Group B Streptococcus (GBS) is a bacterium present in the vagina of approximately 1 in 4 pregnant women. Giving women antibiotics in labour reduces the risk of their babies developing GBS infection. Current UK practice is to offer antibiotics when the baby is at higher risk of developing the infection based on maternal risk factors. This “risk factor” screening is imperfect: some babies born to mothers without risk factors still develop an infection and many women with risk factors do not carry GBS but receive antibiotics unnecessarily. A better solution is “routine testing” of every pregnant woman, and offering antibiotics in labour to those who are carrying GBS.

Who can participate?
All pregnant women giving birth at 24 or more week’s gestation within her maternity unit’s recruitment period.
Up to 50 women over 16 years old at some sites will be asked to take part in the qualitative sub study.

What does the study involve?
We will work with 80 hospitals and birth centres. Hospitals will be randomly allocated to the “risk factor” or the “routine testing” approach. Hospitals allocated to the “routine testing” approach will be further randomly divided into testing women using a swab taken from the vagina and rectum either a) at 35-37 weeks of pregnancy, or b) in labour, using a rapid test kit. Women with a positive test result will be
offered antibiotics in labour. All mothers in preterm labour or who had a previous baby with GBS infection will be offered antibiotics as per current guidance. We will compare the number of babies who develop serious infection born in all “routine testing” hospitals and birth centres with those using the “risk factor” approach. As infections are relatively rare, we will need to collect information on 320,000 women to be able to see a difference between the two main approaches. We will use routinely collected data from national systems to avoid burdening busy clinical staff. We will also interview women and healthcare professionals about the acceptability of the testing approaches. Finally, we will compare the overall costs of each strategy and work out which represents the best value for money for
the NHS.

What are the possible benefits and risks of participating?
The trial does not benefit women directly but the information we get from this trial may help us to treat pregnant women with Group B Streptococcus in future

Where is the study run from?
The trial is managed by the Nottingham Clinical Trials Unit which is part of the University of Nottingham

When is the study starting and how long is it expected to run for?
April 2020 to September 2022

Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme

Who is the main contact?
Sarah Craig
gbs3@nottingham.ac.uk


Trial website

Contact information

Type

Public

Primary contact

Ms Sarah Craig

ORCID ID

http://orcid.org/0000-0003-3946-6329

Contact details

Nottingham Clinical Trials Unit
Building 42
Room A17
University Park
University of Nottingham
Nottingham
NG7 2RD
United Kingdom
+44115 8231608
Gbs3@nottingham.ac.uk

Type

Scientific

Additional contact

Prof Jane Daniels

ORCID ID

http://orcid.org/0000-0003-3324-6771

Contact details

Nottingham Clinical Trials Unit
University of Nottingham
Building 42 Room BO4
University Park
Nottingham
NG7 2RD
United Kingdom
+44115 82 31619
jane.daniels@nottingham.ac.uk

Type

Scientific

Additional contact

Dr Kate Walker

ORCID ID

http://orcid.org/0000-0001-5794-7324

Contact details

Nottingham Clinical Trials Unit
Building 42 Room B03
University Park
University of Nottingham
Nottingham
NG7 2RD
United Kingdom
+441158231581
kate.walker@nottingham.ac.uk

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

42782

Study information

Scientific title

The clinical and cost-effectiveness of testing for Group B Streptococcus: a cluster randomised trial with economic and acceptability evaluations (GBS3)

Acronym

GBS3

Study hypothesis

Does routine testing of women for GBS colonisation either in late pregnancy or during labour reduce the occurrence of early-onset neonatal sepsis, compared to the current risk factor based strategy?

Ethics approval

Approval pending, East Midlands - Derby Research Ethics Committee (The Old Chapel, Royal Standard Place, Nottingham, NG1 6FS; +442071048036; NRESCommittee.eastmidlands-derby@nhs.net), ref: 19/EM/0253, 19/CAG/0139

Study design

Randomised; Both; Design type: Screening, Other, Qualitative

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please email GBS3@nottingham.ac.uk to request a patient information sheet

Condition

Group B streptococcus infection in pregnancy

Intervention

We will work with 80 maternity units. Maternity units will be randomly allocated to the “risk factor” or the “routine testing” approach. Maternity units allocated to the “routine testing” approach will be further randomly divided into testing women using a swab taken from the vagina and rectum either a) at 35-37 weeks of pregnancy, using a lab based test or b) in labour, using a rapid test kit. So all eligible women at the same hospital will receive the same treatment.

Information for the trial will be displayed on posters in the maternity units, and on patient information sheets (Available upon request), and the website. Women will not be routinely given a patient information sheet, and written informed consent will not be received. If the maternity unit has been randomised to routine testing the swab process will be explained to the women, and verbal consent will be sought for taking the swab.

Bedside Test: A swab will be taken from both the vagina and rectum (back passage) whilst the women is in labour. This can be taken by a healthcare professional or the women herself. The procedure will not hurt but it may be slightly uncomfortable. The swab will be put immediately into a machine by a member of the women’s care team and the results will be available within one hour. If the result is positive for Group B Streptococcus, the women will be offered antibiotics during labour.

Lab Based Test: A swab from both the vagina and rectum (back passage) when the women is 35-37 weeks pregnant will be taken. This can be taken by a healthcare professional or by the women herself. The procedure will not hurt but it may be slightly uncomfortable. The swab will be sent to the women’s hospital laboratory for testing and results will be sent to the women within 3 days. If the result is positive for Group B Streptococcus, the women will be offered antibiotics during labour.
Usual care: Sites will follow the current risk factor based screening and treatment approach. The RCOG Greentop Guideline No. 36 states women with the following risk factors for EOGBS infection should be offered IAP:
•Having a previous baby with GBS disease
•Discovery of maternal GBS carriage incidentally during pregnancy
•Preterm birth
•Suspected maternal intrapartum infection, including suspected chorioamnionitis
•Intrapartum raised temperature
•Women colonised in a previous pregnancy should have intrapartum prophylaxis discussed

As infections are relatively rare, we will need to collect information on 320,000 women to be able to see a difference between the two main approaches.

For the main study, routine data about the woman and her baby will be obtained from different NHS databases through NHS digital. This information will have all patient identifiers removed after information has been linked.

If women do not want to take part in the study/don’t want their baby to take part in the study they can do so by the national data opt-out. In all of the maternity units, posters will be displayed explaining the trial, and what it will entail including details of how to opt-out. This information will also be present on the website, and on the patient information sheets, which will be available upon request.

We will also interview some women and healthcare professionals about the acceptability of the testing approaches, via the qualitative sub-study. In 4 maternity units women and healthcare professionals will be asked to take part in the qualitative sub-study. They will be approached by a member of their local usual care team (including local Research Team if local operating policies permit this), or may be able to refer themselves. These women and staff members will be provided with an information sheet and written informed consent will be received before the interviews are undertaken.

We will collect individual-level detailed data for 100 women at each of the 80 sites to inform the economic evaluation of the trial and for monitoring purposes.

Finally, we will compare the overall costs of each strategy and work out which represents the best value for money for the NHS, via the economic evaluation sub-study.

Intervention type

Other

Phase

Drug names

Primary outcome measure

All-cause early neonatal sepsis: either culture-positive (blood or cerebrospinal fluid) or negative/ unknown culture status with ≥ 3 agreed clinical signs or symptoms, for which antibiotics are given for ≥ 5 days, within 7 days of birth

Secondary outcome measures

1. Neonatal:
1.1 Birth weight
1.2 Perinatal mortality
1.3 5 minute Apgar
1.4 Gestational age at birth
1.5 Fetal acidaemia (cord arterial pH <7.05 or first neonatal pH)
1.6 Neonatal specialist care (length of stay, highest level of care)
1.7 Seizures
1.8 Abnormal neurological signs at >24 hours of age (hypotonia or abnormal level of consciousness).
2. Maternal:
2.1 Mode of onset of labour
2.2 Mode of delivery
2.3 Duration of hospital stay
2.4 Change of intended location of childbirth
2.5 Maternal intrapartum anaphylaxis.
3. Process:
3.1 Maternal risk factors for EOGBS infection developing in baby
3.2 Testing coverage
3.3 Testing at appropriate time
3.4 Test result available at least 4 hours before childbirth
3.5 GBS-specific IAP coverage
3.6 Timing of IAP
3.7 Number of doses of IAP
3.8 Proportion of women who tested negative, positive or had no test
3.9 Identified maternal risk factors at all sites
3.10 Declines and acceptances of IAP
3.11 Number of babies of mothers who tested positive for GBS and had IAP commenced
3.12 Observation time following positive GBS result
3.13 Maternal intrapartum or postnatal sepsis
4. Economic:
4.1 Incremental cost per case of early neonatal sepsis avoided as a result of alternative testing strategies for GBS in pregnancy or labour
4.2 Incremental cost per quality adjusted life year gained associated with each strategy, as a result alternative testing strategies for GBS in pregnancy or labour
5. Qualitative:
5.1 Acceptability, barriers and facilitators to implementation, and on the influence of site-specific context and process mechanisms on GBS testing

Overall trial start date

01/04/2019

Overall trial end date

30/09/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

There are eligibility criteria at a site level, which determine which maternity units can participate; at a testing level for women giving birth in testing maternity units; and at a data set level.

1. Inclusion criteria – site level
1.1 Consultant-led maternity units, and alongside midwifery-led units (AMUs) if able to accept women requiring IAP
1.2 Capable of implementing either the antenatal enriched culture or intrapartum rapid testing strategies with training and support

2. Inclusion criteria – testing level
2.1 In ECM units, all women attending an antenatal clinic after 35 weeks’ gestation
2.2 In rapid test units, all women who experience labour or prelabour rupture of membranes at > = 37 weeks’ gestation
2.3 In risk factor units, all women who experience labour or prelabour rupture of membranes at > = 24 weeks’ gestation

3. Inclusion criteria – dataset level
3.1 In all units, all women giving birth > = 24 weeks’ gestation within their unit’s study period, regardless of mode of delivery and all her live born babies
3.2 Women who experience an intrapartum stillbirth will be included as they may have had testing for GBS and GBS may be implicated in the aetiology of their stillbirth

4. Inclusion criteria-qualitative study
4.1 Women will be eligible if they are up to 12 weeks postpartum, 16 years of age or older, and reasonably fluent in English
4.2 Women giving birth in a maternity unit allocated a testing strategy, and not a usual care unit
4.3 Clinicians will be eligible if they are a registered health professional working in an NHS maternity or neonatal service in one of the 4 NHS recruitment sites

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 320,000; UK Sample Size: 320,000

Participant exclusion criteria

1. Exclusion criteria – testing level
1.1 Decline clinical consent to provide a swab
1.2 Previous baby with GBS disease (early or late onset) and who want IAP
1.3 In rapid test units, women who on arrival at the maternity unit are considered likely to deliver they baby within the next hour
1.4 In rapid test units, women in preterm labour (suspected, diagnosed, established), who should be offered IAP routinely
1.5 Known congenital anomaly incompatible with survival at birth, of a singleton or all multiple fetuses
1.6 Known prelabour intrauterine death, of a singleton or all multiple fetuses

2. Exclusion criteria – dataset level
2.1 Congenital anomaly incompatible with survival at birth, of singleton or all multiple fetuses
2.2 Prelabour intrauterine death, of singleton or all multiple fetuses.
2.3 Withdrawal of consent to use data, through the NHS data-opt out

3. Exclusion criteria-qualitative study
3.1 Women will be excluded if their baby died prior to birth or if they lack capacity to give informed consent
3.2 Clinicians will be excluded if they are not currently practising and/or working in an NHS maternity or neonatal service
3.3 Women and clinicians not receiving care or working in the NHS sites taking part in this study will not be eligible

Recruitment start date

01/04/2020

Recruitment end date

01/04/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

-
-
United Kingdom

Sponsor information

Organisation

University of Nottingham

Sponsor details

Research and Innovation
University of Nottingham
East Atrium
Jubilee Conference Centre
Triumph
Nottingham
NG8 1DH
United Kingdom
+44115 84 67906
sponsor@nottingham.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 17/86/06

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The comprehensive project results will be reported in the journal Health Technology Assessment. The individual component studies will be published together or individually in high-impact peer reviewed journals and by presentation at medical and midwifery conferences locally, nationally and internationally.

The datasets generated during and/or analysed during the current study will be available upon request from Nottingham Clinical Trials Unit (ctu@nottingham.ac.uk). Participant level data will not be available, as it is not permitted by the routine data providers under the terms and conditions under which NCTU receives the data.

Intention to publish date

31/12/2022

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

27/08/2019: Internal review. 19/08/2019: Trial’s existence confirmed by National Institute for Health Research (NIHR)