Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03908164 |
| Other study ID # |
2018.0297 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
May 7, 2019 |
| Est. completion date |
May 2021 |
Study information
| Verified date |
November 2020 |
| Source |
St George's, University of London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A multicentre study to evaluate the impact of timing of whooping cough (pertussis)
vaccination in pregnancy, with participants randomised to receive whooping cough vaccination
at one of three time points in pregnancy.
Description:
Pertussis is a highly infectious respiratory illness caused by Bordetella pertussis, which
characteristically causes paroxysms of coughing with an associated inspiratory 'whoop'. In
young infants the clinical presentation can be atypical, is frequently associated with
apnoeic episodes and can cause significant morbidity and mortality. Following the
introduction of pertussis vaccination into routine infant schedules worldwide there was a
significant reduction in the incidence of pertussis. However, recently in a number of
countries, despite high vaccine coverage, there has been a resurgence of pertussis disease
associated with an increase in infant deaths. Various strategies to control the increasing
burden of infant pertussis disease have been considered including cocooning, a strategy in
which close contacts of an infant are vaccinated, a neonatal dose of a pertussis containing
vaccine, the addition of an adolescent dose to the schedule and vaccination in pregnancy. Of
these, the latter has gained most support.
Vaccination in pregnancy is a strategy which relies on effective transport of antibody across
the placenta, a process which depends on the antibody available, the gestation of the
pregnancy and the health of the placenta. In the case of pertussis, the main aim is to
prevent disease in babies (prior to the age of routine vaccination) as they have a higher
mortality than any other age group from pertussis disease.
It is now clear that pertussis vaccination in pregnancy can reduce the burden of disease in
young infants in the period prior to them being fully immunised, and can do so safely.
However, it is not established whether there is an optimal time to vaccinate in pregnancy to
ensure maximal protection of the infant. This is reflected in the different guidelines
currently in place in different countries: in the UK vaccination is advised from 16 weeks
gestation, in Canada from 26 weeks, in the USA from 27 weeks and in Australia from 28 weeks.
While some studies have suggested that vaccination later in pregnancy can achieve higher
antibody concentrations in the newborn, others have found earlier vaccination provides
improved immunity compared to later vaccination. The significance of this is that if earlier
vaccination is shown to be equivalent, there are clear logistical benefits in allowing the
widest possible time window in order to maximise the opportunities for pregnant women to be
vaccinated and thereby improve vaccine coverage.
When the pertussis vaccination in pregnancy programmes were first implemented, vaccination
was recommended in the third trimester (USA 27-36 weeks, UK 28-32 weeks). This decision was
based on the hypothesis that vaccination would be most effective if it was timed to allow the
peak in maternal antibody levels after vaccination to coincide with the time of most
efficient placental transport.
There is a significant lack of agreement on optimal timing of pertussis vaccination in
pregnancy due to conflicting data. This is the rationale for this randomised controlled
trial.
In this study all participants will receive a pertussis containing vaccine licensed for use
in pregnancy. In the UK currently the vaccine used is Boostrix-IPV® manufactured by
GlaxoSmithKline. This vaccine contains pertussis toxin (PT) (8 micrograms), filamentous
haemagglutinin (FHA) (8 micrograms) and pertactin (PRN) (2.5 micrograms) as well as
diphtheria toxoid (not less than 2 international units), tetanus toxoids (not less than 20
international units) and inactivated polio virus types 1-3 (type 1 40 D-antigen unit, type 2
8 D-antigen unit, type 3 32 D-antigen unit). This vaccine will be given at the time period
assigned by randomisation. All possible time periods included in the study are within that
recommended in the UK as part of routine practice.
Participants will have blood sampling prior to vaccination, 14 days following vaccination and
at the time of delivery. At delivery a cord blood sample will also be obtained and an infant
sample taken from the infants of participating women at 28-42 days after completion of their
primary immunisations.
There is a paucity of information about functional immunity of anti-PT antibody in serum and
colostrum/breastmilk following vaccination in pregnancy. We will be investigating this in two
exploratory sub-studies. The first of these (investigation of functional immunity of anti-PT
antibody in serum) will be performed on samples being performed as part of the main study.
For investigation of functional immunity of anti-PT antibody in colostrum and breastmilk we
will ask participants at two participating institutions if they are willing to participate in
a breastfeeding sub-study if they decide to breastfeed. For participants who take part in
this sub-study a sample of colostrum will be obtained within 48 hours of delivery and a
further breast milk sample at 14 days and 5 months following delivery.
