Condition category
Pregnancy and Childbirth
Date applied
04/09/2017
Date assigned
08/09/2017
Last edited
08/09/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
In the UK, 1 in 220 babies are stillborn, which describes a baby born with no signs of life after 24 weeks of pregnancy. Forty percent of babies who are stillborn born die after 36 weeks of pregnancy and have no lethal structural abnormality. If these babies could be identified and delivered earlier, lives could be saved. The association between a woman’s perception of a reduction in her baby’s movement and stillbirth is well documented. Reduced fetal movement is thought to be a symptom of nutrient or oxygen restriction and is related to changes in placental structure and function. Other research suggests that adding a blood test to determine how well the placenta is working might help professionals make decisions about when to intervene to prevent complications. Currently, it is not known whether additional tests of the placenta can reduce the risk of pregnancy complications for both mothers and babies. This study involves women having an additional blood test to measure how well their placenta is working. The results of the blood test will help clinicians decide how to treat women with reduced fetal movement compared with standard care. This is a pilot trial to provide initial information about whether the blood test is helpful in making clinical decisions. A much larger research study will then be needed to assess this properly.

Who can participate?
Women aged 16 and older who are between 36 to 41 weeks pregnant who have reduced fetal movement.

What does the study involve?
Participants are randomly allocated to one or two groups. All participants will have a blood sample taken. Those in the first group have their blood sample tested immediately and the result acted upon. Those in the second group do not have their blood sample tested immediately and so the result will not be available and therefore cannot be acted on. All participants are followed up with questionnaires.

What are the possible benefits and risks of participating?
There are no direct benefits with participating. There is a risk of discomfort when blood samples are taken.

Where is the study run from?
This study is being run by University of Nottingham (UK) and takes place in hospitals in the UK.

When is the study starting and how long is it expected to run for?
July 2013 to February 2019

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
1. Professor Alexander Heazell
2. Dr Lindsay Armstrong-Buisseret
remit2@nottingham.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Dr Lindsay Armstrong-Buisseret

ORCID ID

Contact details

Nottingham Clinical Trials Unit
School of Medicine
University of Nottingham
Room C2000
NHSP
C Floor
South Block
Queen’s Medical Centre
Nottingham
NG7 2UH
United Kingdom
+44
remit2@nottingham.ac.uk

Type

Scientific

Additional contact

Prof Alexander Heazell

ORCID ID

http://orcid.org/0000-0002-4303-7845

Contact details

Maternal and Fetal Health Research Centre
5th Floor (Research)
St Mary’s Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
-
Alexander.Heazell@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

33384

Study information

Scientific title

Reduced Fetal Movement Intervention Trial (ReMIT-2): A multicentre, randomised controlled pilot trial of standard care informed by results of an additional placental factor blood test versus standard care in women presenting with reduced fetal movement (RFM) at or after 36+0 weeks gestation

Acronym

ReMIT-2

Study hypothesis

The addition of a biochemical test of placental function will better identify pregnancies at high risk of complications after women present with reduced fetal movement at or after 36+0 weeks gestation. Therefore, intervention based upon a biochemical test is hypothesised to improve perinatal outcomes.

Ethics approval

North West – Greater Manchester West Research Ethics Committee, 13/01/2017, ref: 17/NW/0014

Study design

Randomised; Interventional; Design type: Diagnosis, Prevention, Management of Care

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Specialty: Reproductive health and childbirth, Primary sub-specialty: Maternal/ Fetal medicine; UKCRC code/ Disease: Reproductive Health and Childbirth/ Other disorders originating in the perinatal period

Intervention

Eligible participants are randomised in a 1:1 ratio to either the intervention arm or the control arm. Randomisation is stratified by site and number of weeks gestation when the participant first presents at hospital (<40 weeks gestation or ≥40 weeks gestation). The randomisation schedule is based on a computer generated pseudo-random code using random permuted blocks of randomly varying size, created by NCTU in accordance with their standard operating procedure (SOP) and held on a secure University of Nottingham server.

Intervention arm:
Participants in this arm receive the standard care. Participants provide an extra blood sample taken to measure the soluble-fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) ratio. The sample is tested immediately and the results are acted upon by site staff.

Control arm:
Participants in this arm receive the standard care. Participants provide an extra blood sample taken to measure the sFlt-1/PlGF ratio but the sample is not tested immediately so the result is not be available to site staff or the participant and therefore cannot be acted on.

For participants not involved in the Midwife-Led Interview, the follow-up period from delivery to completion of the participant questionnaires is ~10 weeks. For the sub-group of participants involved in the Midwife-Led Interview, the follow-up period from delivery to completion of the interview is ~16 weeks.

Intervention type

Other

Phase

Drug names

Primary outcome measures

ReMIT2 is a pilot feasibility trial and therefore does not have primary and secondary outcomes like a standard drug trial. There are feasibility outcomes which determine the feasibility of doing a large main trial based on results collected in ReMIT2 and there are proof of concept outcomes which address whether the intervention might have an effect on neonatal outcome or healthcare costs.

Feasibility outcomes:
1. Number of potentially eligible women at each site and number of women recruited at each site as collected from hospital records at the time women attend with RFM throughout recruitment period.
2. Proportion lost to follow-up after discharge from hospital and reasons for loss to follow-up as collected from hospital records at the time site confirms participant is lost to follow-up.
3. Spectrum of clinical characteristics of women at randomisation (frequency of small for gestational age (SGA) fetuses, obstetric history, nulliparous) as collected from patient medical records at randomisation.
4. Reasons for non-recruitment, if available as collected from hospital records of women who attend with RFM throughout recruitment period.
5. Compliance with the trial interventions and reasons for non-compliance as collected from patient medical records at the time the trial intervention is delivered.
6. Completeness of data collection for planned outcomes in the main trial including that needed for health economic analyses as measured using the SF12 questionnaires at baseline and ~6 weeks after birth, plus a Health Resource Questionnaire at ~ 6 weeks after birth.
7. Views of women about participation collected ~6 weeks after birth using a Participant Views questionnaire.
7.1. A sub-group of participants will be interviewed ~16 weeks after birth to gain further insight into their views of the trial using a semi-structured interview guide.
8. Views of clinicians on the trial collected 9-12 months after site initiation using a Health Professional Views questionnaire.

Secondary outcome measures

Proof of concept outcomes:
1. Frequency of induction of labour or planned caesarean and reasons for these procedures as collected from patient medical records at the time of the baby’s birth
2. Neonatal outcome including:
2.1. Stillbirths and deaths before discharge as collected from patient medical records at the time of the baby’s birth
2.2. Five minute Apgar score of <7 as collected from patient medical records at the time of the baby’s birth
2.3. Umbilical artery pH <7.05 as collected from patient medical records at the time of the baby’s birth
2.4. Admission to the neonatal unit for >48 hours as collected from patient medical records at the time the baby is discharged from the neonatal unit
2.5. SGA (<10th centile on neonatal birthweight standards) as collected from patient medical records at the time of the baby’s birth
2.6. Use of therapeutic cooling as collected from patient medical records during the time the baby is on the neonatal unit
2.7. Length of stay in hospital. Collected from patient medical records at the time of the baby’s discharge from hospital
2.8. Duration of respiratory support as collected from patient medical records during the time the baby is on the neonatal unit
2.9. Number of dependency days on neonatal unit as collected from patient medical records during the time the baby is on the neonatal unit
3. Maternal hypertensive disorders defined as development of gestational hypertension or pre-eclampsia as collected from patient medical records prior to baby’s birth
4. Maternal deaths prior to discharge as collected from patient medical records prior to discharge from hospital
5. Maternal admissions to Intensive Care Unit (ICU) as collected from patient medical records prior to discharge from hospital
6. Change in Generalised Anxiety Disorder 2 (GAD-2) scale measured at enrolment and ~6 weeks after birth
7. Quantifiable impact on costs and outcomes incurred by delivering the intervention from an NHS perspective and as assessed by the SF-12™ Health Survey measured at enrolment and ~6 weeks after birth along with a Health Resource Use questionnaire measured ~6 weeks after birth
8. The diagnostic performance of the placental factor test in participants allocated to the control arm of the trial as measured by central laboratory analysis using a Roche Cobas plus sFlt-1 and PlGF kits

Overall trial start date

31/07/2013

Overall trial end date

28/02/2019

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women presenting with RFM before the onset of labour between 36+0 and 41+0 weeks gestation (assessment of gestation will be based on the best available information which will usually be the first or dating scan)
2. Viable singleton pregnancy on initial assessment
3. No indication for immediate delivery as assessed by CTG and ultrasound scan
4. Provision of written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 750; UK Sample Size: 750

Participant exclusion criteria

1. Maternal age < 16 years
2. Fetus known to have any of the following congenital anomalies as per the Fetal Anomalies Screening Programme (FASP):
2.1. Anencephaly
2.2. Open spina bifida
2.3. Cleft lip
2.4. Diaphragmatic hernia
2.5. Gastrochisis
2.6. Exomphalos
2.7. Serious cardiac abnormalities
2.8. Bilateral renal agenesis
2.9. Lethal skeletal dysplasia
2.10. Edward’s syndrome (trisomy 18)
2.11. Patau’s syndrome (trisomy 13)
2.12. Any other severe structural abnormality
3. Multiple pregnancy
4. Women for whom it is their first attendance to ANY antenatal care e.g. “unbooked” women
5. Previous randomisation into the ReMIT-2 trial in this pregnancy
6. Concurrent participation in the intervention phase of another clinical trial which determined the timing or mode of delivery

Recruitment start date

15/10/2017

Recruitment end date

31/12/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St Mary’s Hospital
Hathersage Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane North Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

University Hospital Coventry
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom

Trial participating centre

John Radcliffe Hospital
University of Oxford Level 3 Women’s Centre
Oxford
OX3 9DU
United Kingdom

Trial participating centre

St George’s Hospital
Fetal Medicine Unit 4th Floor Lanesborough Wing St George’s University Hospitals NHS Foundation Trust Blackshaw Road Tooting
London
SW17 0QT
United Kingdom

Trial participating centre

Liverpool Women’s Hospital
Department of Women’s and Children’s Health Liverpool Women’s Hospital Crown Street
Liverpool
L8 7SS
United Kingdom

Trial participating centre

Sunderland Royal Hospital
Maternity Unit Kayll Road
Sunderland
SR4 7TP
United Kingdom

Trial participating centre

James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom

Trial participating centre

Warwick Hospital
Lakin Road
Warwick
CV34 5BW
United Kingdom

Trial participating centre

University Hospital of North Tees
Hardwick Road
Stockton-on-Tees
TS19 8PE
United Kingdom

Sponsor information

Organisation

The University of Manchester

Sponsor details

Oxford Road
Manchester
M13 9PL
United Kingdom
+44 161 275 2725
Research.Governance@manchester.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed journal. Planned publication of the study protocol.

IPD sharing statement:
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

28/02/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes