Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04008485 |
| Other study ID # |
STH19385 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2018 |
| Est. completion date |
October 31, 2021 |
Study information
| Verified date |
November 2023 |
| Source |
Sheffield Teaching Hospitals NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Every year, globally, about 15 million babies are born preterm (before 37 weeks). This number
is rising. Preterm birth (PTB) complications are the leading cause of death among children
under 5 years of age, responsible for nearly 1 million deaths annually. PTB poses a strain on
scarce health resources: each very premature baby costs tens of thousands of pounds in
newborn care. One in 4 babies born before 28 weeks develop neurological impairment, a parent
often having to give up work to care for an affected child. The prediction and prevention of
PTB remain challenging because current methods, such as measuring the cervix by ultrasound,
have limited accuracy. If a technique that reliably predicts PTB could be developed, there
are care measures that can be employed to delay birth to reduce long-term
disability/impairment. The Investigators have been studying whether they can detect the
changes in cervical tissue structure and composition that precede PTB by using very low
current Electrical Impedance Spectroscopy (EIS). Evidence recently showed that women at high
risk of PTB (history of previous PTB), who deliver preterm, including delivery before 28
weeks gestation, have lower cervical "resistance" in mid-pregnancy than those who deliver at
term. With NIHR funding, the investigators have developed a new device, based on a technique
called magnetic impedance spectroscopy (MIS) that should address limitations of the EIS
device for assessing PTB risk. The investigators now want to refine the new MIS device by
minimising the signals it receives from other tissues around the cervix and making its
measurements at internal body temperature more stable. The researchers also conduct clinical
experiments to test whether it predicts PTB better than the previous EIS device, and check
whether pregnant women find its use acceptable. This information will allow them to obtain UK
regulatory approval to test the device in larger trials.
Description:
The studies will be undertaken at the Jessop Wing (JW) Maternity Unit of the Royal
Hallamshire Hospital, a tertiary referral unit with annual birth statistics of approximately
8000 births per annum. The JW receives in utero transfers from > 6 other hospitals in South
Yorkshire and houses the regional neonatal intensive care unit with high dependency care
facilities equipped to deal with extremely premature births, including those born at
gestational ages borderline for viability (23-26weeks). The unit is therefore suited for the
care of women at high risk of premature delivery and is well suited to house this study. The
clinician on the core research team for this application also accepts referrals for high risk
antenatal care and surveillance of women most at risk of premature delivery from colleagues
in referring hospitals.
To reach this objective, the Investigators will package the project into three work packages
(WP) with target milestones over 36 months. The time frames for the study phases are outlined
below.
WP1. DURATION - 30 MONTHS, M1-30. LEAD J. HEALEY
Objectives:
- To recruit high-calibre research staff (Postdoctoral Research Associate Clinical
Engineer and Clinical Research Fellow) at project initiation.
- To refine/optimise the hardware and software of the MIS device to enable a clinical
grade version - the MIS Mark 2 device (in collaboration with Arrow Technical).
- To apply for MHRA regulatory approvals for a device that can be employed for follow-on
multicentre studies, towards eventual CE Marking post-project.
Outline of work strands in WP1. Improvements on current MIS 1 device prototype that will be
addressed during this work package (M1-M9) include the following:
1. Removal of measurement artefacts
2. Removal of probe handling sensitivity from perturbations of the electric field around
the probe
3. Reduction in thermal drift by better choice of materials and coil assembly and the use
of "mechanical chopping" of the magnetic field
4. Reduction of power dissipation in the probe in order to improve stability 5. Improving
the ruggedness of the probe to cope consistently with clinical use 6. Fractionally
reducing the probe diameter.
These will culminate in refinements to the device hardware and software (M8-9). The
Investigators will also simultaneously consolidate the technical documentation, which have
been systematically collected during the development of the MIS Mark 1 device (M1-M18), and
submit an application to the MHRA for regulatory approvals by M19. Following iterations with
the MHRA they anticipate obtaining final approvals by the MHRA by the end of this workpackage
(M30).
PPI Input to WP1
- The Investigators will schedule their first PPI meeting in Month 3 - this meeting will
include an induction programme for new PPI members, as well as a refresher session for
current PPI members. The PPI group will deliberate on the research plan and the
participant information leaflets and consent forms for the clinical studies that will be
submitted for National Research Ethics Committee approvals.
o This PPI meeting has successfully held on 27 April 2017
- A second PPI meeting in Month 11 will review project progress, consider the Mark 2 MIS
device and advice on the planned submission to the MHRA.
WP1 Deliverables:
- Prompt initiation of project following successful pre-project employment of PDRA and
Clinical Research Fellow.
- 1st PPI meeting Month 3.
- Manufacture of high-performance Mark 2 MIS cervical device by M10
- 2nd PPI meeting Month 11
- Submission of initial application for regulatory approvals by the MHRA by M19
- MHRA Regulatory approvals secured by M30 WP2. DURATION - 30 MONTHS, M 1- 30. LEAD PROF
DILLY ANUMBA
Objectives:
During this phase, the Investigators will conduct clinical experimental studies to determine
the predictive potential of the MIS Mark 2 device for preterm birth (PTB) in a cohort of
asymptomatic women at risk of PTB (previous history of PTB, AHR) attending for pregnancy care
(n=100), and another cohort of women (n=100) presenting to labour ward between 20-34 weeks
with symptoms of preterm labour (regular uterine contractions - > 1 contraction every 10
minutes - but cervix less than 4 cm dilated, SYM). The rationale for sample size estimates is
clarified later on this protocol.
Outline of work strands in WP2:
This WP will overlap with WP1 to ensure that technical project development occurs in tandem
with the preparation for, and execution of, clinical experimental studies.
During this WP the Investigators will:
- Obtain research ethics and governance approvals (M1-M6).
- Generate preliminary data (M7-M18) that will be employed to: a) apply to the MHRA for
regulatory approvals, and b) optimise the probe hardware and software further, and
- Conduct experimental studies on the cohorts detailed above (M8-M30) - recruit and study
asymptomatic HR cohort (n=100) and symptomatic cohort (n=100) from M8 -M30 (22 months).
In addition to standard care, the women will have an ultrasound scan to assess cervical
length, vaginal swab specimen collection for fetal fibronectin determination and
microbiological studies and MIS assessment at each of two study visits. Women with
abnormal cervical cytology in the previous 3 years or with signs of ongoing cervical
infection will be excluded from the studied.
Study conduct details:
• Target population and sample selection: Asymptomatic high-risk women. These participants (≥
16 years of age) will have had no signs of cervical infection, no previous cervical surgery,
and will have had a normal cervical smear within the previous 3 years. Prospective
participants will be approached at their first hospital antenatal visit. The study will be
explained and study materials provided. The participants will be asked to contact research
staff by telephone or through their community midwife, or at the time of the participant's
next attendance to the prematurity clinic or ultrasound scan appointment if the women wishes
to participate. Written informed consent will then be obtained by research staff who will
also conduct the two study visits. Women will be scheduled to attend for MIS measurement at
20-22 weeks, to be repeated at 26-28 weeks. This measurement will be taken at the same time
as the routine examination which the participants receive when they attend the prematurity
clinic. At each study visit the patient will undergo a vaginal examination. Triple high
vaginal swabs will then be taken for bacteriology and fetal fibronectin. The sterile magnetic
impedance probe will then be introduced, data being captured automatically by pressing the
data capture button on the handle of the device. A transvaginal scan will also be performed
to measure CL. The average duration of this assessment, from obtaining the swabs to
completing the ultrasound scan, is about 7 minutes.
The above procedure will be carried out at each of the two study visits planned. Women
attending the prematurity clinic are seen on average every two to three weeks. Consequently,
cervical magnetic impedance spectroscopy measurements will not need to be measured at every
hospital visit.
Symptomatic pregnant women. These women (≥ 16 years of age) will be approached when the
participant attends the labour delivery room or triage with symptoms of preterm labour as
detailed above. As a matter of clinical routine these women receive a speculum examination,
triple vaginal swabs taken, and fetal fibronectin and cervical length scans as indicated. The
study will be explained to them and study materials provided. The participants will be asked
to contact research staff by telephone or through their clinical midwife if the participants
wish to participate. The participant will be given time to decide. If the participant agrees
to take part, written informed consent will then be obtained by research staff who will also
conduct the MIS study. If clinical assessments have not already been performed by the time of
obtaining consent the participant will be carried out at the same time
