Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04098341 |
| Other study ID # |
IRAS247388 REC19/LO/0557 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 3, 2019 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
January 2023 |
| Source |
Queen Mary University of London |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The UK has the second highest tuberculosis (TB) incidence in Western Europe. Most active
cases occur in migrants due to reactivation of latent TB infection (LTBI) acquired abroad.
Screening migrants for LTBI was recently introduced by Public Health England to reduce TB
rates and transmission of infectious cases. Newham, which has one of the highest TB rates in
London introduced the first large-scale LTBI screening programme for migrants, but it is
poorly accessed by pregnant women and screening uptake is low. The issue of how best to
screen for TB during pregnancy is important because pregnant/ postpartum women are at
particularly high risk of developing TB, and migrants from countries with high TB rates may
only interact with healthcare services during pregnancy.
Effective strategies are urgently needed to improve screening uptake for LTBI in pregnant
migrants. The Antenatal clinic is an attractive location to screen for LTBI because uptake
and acceptability of opt-out screening for other infectious diseases (HIV) is high. We will
evaluate the uptake, effectiveness and acceptability of routine screening for LTBI in
antenatal clinics. Eligible patients are pregnant women who have entered the UK within 10
years from a country with TB rates of >150/100,000. Screening will involve a blood test,
taken with other routine antenatal blood tests. We expect that in this setting, screening
will be acceptable and uptake will be high. Our main outcome will be to assess the uptake of
screening in at least 200 women. Acceptability of screening and understanding barriers of
healthcare professionals to test for LTBI are secondary aims. The study will provide
important information about a new setting in which to screen pregnant migrants for LTBI and
barriers to starting treatment postpartum, which will inform the definitive trial to guide
national policy on LTBI screening in antenatal care.
Description:
The UK has the second-highest TB incidence in Western Europe. Most active TB cases occur in
the non-UK born population (migrants) in large cities such as London. Migrants most at risk
of TB are from countries with a high TB incidence such as the Indian subcontinent and
Sub-Saharan Africa. One quarter of the whole world population are estimated to have LTBI.
Migrants who have acquired LTBI outside the UK, often reactivate in the first 5-10 years
after arrival. Barts Health NHS trust has one of the highest number of TB notifications in
England and manages 8% of active TB cases in the UK.
Many countries in SE Asia and Africa, which have the highest global TB burden, also have high
maternal mortality rates. In women of reproductive age (15-45 years), TB is now among the
three leading causes of death. In 2014, an estimated 480,000 women died as a result of TB
globally. TB diagnosis in pregnancy is often delayed even in low-incidence countries.
Pregnancy can mask the clinical manifestations of TB, as some of the symptoms of TB such as
fatigue and loss of appetite are also common in pregnancy itself. There is a high risk of
LTBI reactivation during pregnancy and postpartum likely due to T-cell suppression and
reduced interferon-gamma production.There is an elevated risk of TB during pregnancy and
immediately postpartum compared to the general population. TB in pregnancy carries a high
risk of perinatal complications, poor foetal and maternal outcomes and early diagnosis of TB
is important to prevent significant maternal and perinatal complications. A simple clinical
algorithm recommended by the WHO based on absence of current cough, fever, weight loss, and
night sweats can help to exclude active TB disease. Sputum smear has a low sensitivity for
diagnosis of active TB in pregnancy, however health care professionals will have a higher
index of suspicion for active TB in IGRA positive pregnant women presenting with symptoms
suggestive of TB, thus preventing a delay in diagnosis. TB diagnosis in pregnancy can be
delayed due to reduced awareness among health care providers and reluctance to investigate
non-specific TB symptoms by chest radiography. Pregnant migrants may not be accessing routine
health care and often do not have a GP. Antenatal care may therefore be a rare and critical
opportunity to assess a woman's health and screen for TB. Moreover, antenatal care provides
an opportunity for health promotion such as advocating GP registration. England's
collaborative TB strategy recommends migrant screening for LTBI in high incidence areas in
England including boroughs such as Newham. LTBI screening programmes have now been
implemented. Between April 2015 and June 2016, 5,622 eligible migrants in England were
offered an LTBI test, 2,904 (51%) of whom attended for the test. Newham was the first London
borough to introduce a large-scale LTBI screening programme. A total of 20,905 LTBI tests
were reported between July 2014 and June 2017 across England, nearly half of the tests were
reported in Newham however uptake of screening remains low. This may be because individuals
eligible for screening do not have symptoms and perceive the risk of developing active TB as
low. Newham data has shown that uptake of screening varies significantly amongst GP surgeries
indicating that uptake may be influenced by healthcare providers' knowledge and attitudes to
screening but may also be due to other factors such as proximity to phlebotomy services. Data
from the Clinical Effectiveness Group (CEG) at QMUL has shown that in pregnant migrant women
screening uptake is even lower, <25% and this may be because pregnant women have not been
told that LTBI screening is important. There is limited qualitative research about the
acceptability to women of LTBI screening in pregnancy. Reasons for low uptake may be due to
stigma of having active TB or fear of a positive test result affecting their immigration
status. An opt-out approach normalises screening that otherwise may present barriers in
relation to stigma.
Provider knowledge and understanding of the risks of TB screening and treatment is a major
predictor of successful management of TB. Newham data has shown that offer of screening
varies significantly amongst GP surgeries indicating that health care provider knowledge and
attitude may influence offer of screening.
Evaluating the impact of healthcare provider training to improve TB management has mainly
been performed in low income countries and there are only a few rigorous TB training
evaluation studies available. E-learning modules use pre- and post- training tests to
evaluate acquired knowledge. A GP E-learning module has been developed by TB Alert to enhance
knowledge of GPs responsible for screening and treatment of LTBI but the effectiveness of the
module has not been formally evaluated.
Aim of the feasibility study The investigator's aim is to assess whether it is feasible and
acceptable to screen an at-risk migrant population for latent tuberculosis infection (LTBI)
at routine antenatal booking visits in secondary care, using opt-out Interferon- gamma
release assay (IGRA) testing. This will allow the investigators to develop a definitive large
scale cluster randomised controlled trial (RCT) to evaluate the effectiveness of acceptable
interventions to maximise migrant screening for LTBI in pregnancy, and to increase uptake of
LTBI treatment postpartum.
Primary objective:
To obtain
Real time continuous data on study design:
- Numbers and proportions of pregnant migrant women eligible for opt-out screening with an
IGRA blood test for LTBI in the antenatal care setting.
- The proportion of eligible women who are offered opt-out LTBI screening by healthcare
providers.
- Rate of uptake of the opt-out IGRA blood test screening for LTBI, i.e. the percentage of
women offered who have the test performed.
Credible understanding of study process:
- Information on the feasibility and practicality of the data collection for the
assessment of LTBI at baseline and subsequent visits.
- The appropriate level of support needed for health care providers at site-level to
ensure successful recruitment.
Secondary objective
- Preliminary estimates of disease burden to inform the definitive study
- To identify the characteristics of pregnant women associated with accepting LTBI
screening.
- To estimate the prevalence of active TB and LTBI in the pregnant migrant cohort.
- Assessment of acceptability of opt-out testing and perceptions about screening for LTBI
- To assess participants' perceptions of the TB and LTBI screening process.
- To determine if IGRA testing is an acceptable intervention to be performed using an
opt-out approach in antenatal clinics.
- To evaluate facilitators and barriers to the uptake of LTBI screening among pregnant
migrant women and to identify what type of intervention might be effective in increasing
awareness.
- To assess participants' perception of the risks and benefits of LTBI screening, and any
LTBI treatment, to themselves and their babies.
- To assess participants' perceptions of the timing of treatment (during pregnancy,
post-delivery or after termination of breast feeding).
- To understand health care providers' experiences of the screening process and perceived
barriers and facilitators to screening uptake.
- To assess participants and heath care providers views on implementation of interventions
such as text messaging to increase uptake of LTBI screening and treatment.
To develop acceptable interventions to increase TB awareness among pregnant migrants and
health care providers, thereby increasing uptake of screening, such as
- Educational materials or approaches co-developed with TB Alert to increase knowledge
about signs and symptoms of TB among pregnant migrant women.
- E-learning modules for midwives and other health care providers to increase knowledge
about TB and LTBI.
To collect relevant cost data to assess the cost- effectiveness of LTBI screening in
antenatal care compared to screening in primary care in future definitive trial.
• To test the feasibility of collecting cost data
Definitive trial objectives Primary objective
• To evaluate the effectiveness of interventions to increase uptake of migrant screening for
LTBI in pregnancy
Secondary objectives
- To study the effectiveness of interventions to increase uptake of LTBI treatment
postpartum.
- To evaluate the safety and timing of LTBI treatment postpartum - immediately postpartum
or after cessation of breast feeding
- To determine cost-effectiveness of LTBI screening in antenatal care by preventing cases
of active TB.
Study design
Consent Posters will be displayed in antenatal clinics explaining the study. All patients
will be given a Patient Information Sheet by their midwives that explains the study and what
participation will entail.
Valid implied consent will be used for participation in the study and data collection.
Written informed consent will be taken for LTBI questionnaires, interviews and focus groups.
Furthermore written informed consent will be obtained for questionnaires, knowledge quiz,
interviews and focus groups from healthcare providers participating in the study.
Data collection Basic data on age, ethnicity, socioeconomic status, and substance misuse and
pre-existing medical conditions (such as diabetes) and antenatal history and TB history will
be recorded in all patients electronically in antenatal care according to existing protocols
as part of standard of care.
Setting Antenatal clinics at Royal London Hospital, Whipps Cross University Hospital and
Newham University Hospital.
Planned intervention
Study Intervention All women who are eligible for LTBI screening and attend the antenatal
clinic for their dating scan will be asked to be tested for LTBI alongside other routine
investigations for blood borne viruses. IGRA testing will be offered on an opt-out basis
similar to HIV testing. In addition, all migrants will be screened for active TB by their
midwives using a standardized symptom assessment questionnaire that includes the WHO
recommended TB symptom screen. TB awareness-raising will be delivered in antenatal clinics by
midwives, utilizing evidence-based tools created by TB Alert. Pregnant women will also be
asked to complete a short questionnaire on acceptability of LTBI screening, knowledge about
TB/LTBI, and barriers to screening. At the end of pregnancy, women will be asked again to
complete a questionnaire to compare the perception and knowledge of active TB/LTBI before and
after the screening intervention.
Pregnant women with LTBI will be closely monitored for active TB during pregnancy by their
midwives. The GP will be informed of a positive IGRA test and also the TB clinic will be
notified. The GP will be asked to refer the patient to TB clinic for LTBI treatment or if the
woman lives in Newham she will be treated in primary care. In case this does not happen, the
TB clinic will send a reminder to the GP to refer the patient. If women develop symptoms of
active TB, the midwife will arrange referral to the TB clinic.
Health care providers involved in antenatal care will be asked to complete an E-learning
module on active TB/ LTBI which will be developed by TB Alert and the Royal College of
Midwives. The E-learning course, which will be CPD accredited, has a pre and post-course quiz
to assess any change in knowledge. Health care providers will be also asked to take part in
interviews, focus groups and to complete a questionnaire for which the investigators will
obtain written informed consent.
