Condition category
Pregnancy and Childbirth
Date applied
18/05/2016
Date assigned
19/05/2016
Last edited
04/01/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pre-eclampsia (PE) is a medical condition which can develop during pregnancy, and can affect both the mother and unborn baby. The exact cause of PE is not known, however it is thought to happen because of a problem with the placenta. The placenta is a specialised organ which connects the mother’s blood supply to the baby’s, providing the baby with food (nutrients) and oxygen. In PE, it is thought that the blood supply to the placenta is reduced, which can mean the unborn baby does not get enough nutrients to develop properly. The key indicators of PE are high blood pressure and protein in the mother’s urine. In order to identify as many cases as possible, all women have their blood pressure and urine monitored throughout pregnancy. If PE is diagnosed, the only cure is to deliver the baby. If this occurs before 37 weeks of pregnancy, the mother may need to be admitted to hospital for blood pressure treatment and monitoring for complications, whilst planning for safe delivery of the baby. Some women become unwell very quickly and need to have their babies delivered, while others have long stays in hospital for monitoring. It is not always possible to identify women at high risk of the severe complications of pre-eclampsia needing early delivery. This study will look at levels of a protein produced by the placenta called Placenta Growth Factor (PlGF). Previous studies have shown that women with very low PlGF levels are at greater risk of severe PE and stillbirth. The aim of this study is to find out whether measuring PIGF is a good predictor of PE

Who can participate?
Women who are between 20 and 36 weeks pregnant with suspected PE

What does the study involve?
All participants give an extra sample of blood at the time of assessment by their doctor or midwife for a PlGF blood test. The result of the test is revealed to the clinician at a randomly allocated timepoint, when the clinicians may then use the revealed result to help determine the management of the pregnancy, to help plan care for the participant. Participants at high risk of adverse events may receive intensive assessment and admission, and those at low risk are reassured and returned to routine care.

What are the possible benefits and risks of participating?
There are no anticipated risks to those taking part in the study.

Where is the study run from?
1. Guy’s and St Thomas’ NHS Foundation Trust (UK)
2. St George’s University Hospitals NHS Foundation Trust (UK)
3. Kingston Hospital NHS Foundation Trust (UK)
4. West Middlesex University Hospital (UK)
5. Central Manchester University Hospital NHS Foundation Trust (UK)
6. Liverpool Women’s NHS Foundation Trust (UK)
7. Leeds Teaching Hospitals NHS Trust (UK)
8. Bradford Teaching Hospitals NHS Foundation Trust (UK)
9. Royal United Hospitals Bath (UK)
10. North Bristol NHS Trust (UK)
11. University Hospitals Bristol NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
April 2016 to March 2018

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

Who is the main contact?
Dr Kate Duhig

Trial website

Contact information

Type

Public

Primary contact

Dr Kate Duhig

ORCID ID

Contact details

Womens Health
St Thomas' Hospital
London
SE1 7EH
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

30737

Study information

Scientific title

PARROT - Placental growth factor to Assess and diagnose hypeRtensive pRegnant wOmen: a stepped wedge Trial

Acronym

PARROT

Study hypothesis

The aim of this study is to compare the time it takes from presentation with suspected pre-eclampsia to a confirmed diagnosis with the addition of Placental Growth Factor (PlGF) testing as compared to conventional practice.

Ethics approval

South London Research Ethics Committee, 21/01/2016, ref: 15/LO/2058

Study design

Stepped-wedge designed multicentre randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

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

Condition

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

Intervention

The trial is a stepped-wedge cluster randomisation trial, and all units will begin recruiting to the ‘not revealed’ phase at the trial beginning. The step-lengths are 5 weeks, with a new site chosen at random to transition to become ‘revealed’ to the test at each step.

In the 'not revealed' phase, all women presenting with suspected preeclampsia will be consented for a blood test, the result of which is not revealed to the clinician, and women are managed according to NICE guidelines on the management of hypertensive disorders of pregnancy (NICE 2010).

After transition to the 'revealed' PlFG testing at the randomly allocated timepoint, the clinicians may use the revealed PlGF result as additional information to inform the clinical picture and determining antenatal care incorporated into NICE guidelines.

Those at high risk of adverse events may be streamlined for intensive assessment and admission, and those at low risk reassured and returned to routine antenatal surveillance.

Follow up for all patients is to postnatal discharge of both mother and baby.

Intervention type

Other

Phase

Drug names

Primary outcome measures

Time from first presentation with hypertension to antenatal services to having a confirmed, documented diagnosis of pre-eclampsia (as defined by ISSHP 2014 statement). The time points of evaluation are first presentation with suspected disease to confirmed diagnosis of pre-eclampsia. This is a participant level outcome.

Secondary outcome measures

Added 04/01/2017:
Secondary short-term maternal outcomes:
1. Test performance of the PlGF (vs. currently utilised tests) for clinically indicated delivery for diagnosed pre-eclampsia within 14 days
2. Systolic blood pressure ≥160 mmHg
3. Progression to severe pre-eclampsia (as defined by ACOG)
4. Placental abruption
5. Mode of onset (spontaneous, induced or pre-labour caesarean section)
6. Mode of delivery (spontaneous vaginal delivery, assisted vaginal delivery, caesarean section)

Additional descriptive secondary short-term maternal/fetal outcomes:
1. Maternal death
2. Use of anti-hypertensive drugs
3. Eclampsia
4. Disseminated intravascular coagulation
5. Pulmonary oedema
6. Antepartum haemorrhage
7. Postpartum haemorrhage
8. Estimated fetal weight (on ultrasound scan) <10th centile post-enrolment
9. Absent or reversed end diastolic flow (on umbilical artery Doppler) post-enrolment
10. Primary and additional indications for delivery (maternal hypertension not controlled by maximal therapy, biochemical abnormality, haematological abnormality, fetal compromise on ultrasound scan, fetal compromise on cardiotocography, severe maternal symptoms, 37 weeks’ gestation or specified other)

Secondary short-term perinatal outcomes:
1. Gestational age at delivery
2. Stillbirth
3. Neonatal death prior to hospital discharge
4. Preterm birth (<37 weeks’ gestation)
5. Neonatal unit (NNU) admission for at least 4 hours
6. Birth weight
7. Birth weight centile
8. Apgar scores at 5 minutes post birth

Additional descriptive secondary short-term perinatal outcomes:
1. Necrotizing enterocolitis (Bell’s stage 2 and 3)
2. Retinopathy of prematurity
3. Intraventricular haemorrhage
4. Umbilical arterial pH at birth
5. Need for supplementary oxygen prior to discharge
6. Need for ventilation support (CPAP/high flow/endotracheal ventilation)
7. Abnormal cerebral ultrasound scan
8. Confirmed sepsis (positive blood or cerebrospinal fluid cultures)
9. Seizures (confirmed by EEG or requiring anticonvulsant therapy)
10. Encephalopathy grade (worst at any time: mild, moderate, severe)
11. Other indications and main diagnoses resulting in NNU admission for at least 4 hours

The timepoints of evaluation of the secondary outcomes are taken at the clinic visits, during admission for delivery up to discharge home of mother and infant.

Overall trial start date

01/04/2016

Overall trial end date

31/03/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Women between 20+0 and 36+6 weeks’ of gestation 
2. Suspected pre-eclampsia 
3. Viable fetus
4. Singleton 
5. Aged 18 years or over
6. Able to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 504; UK Sample Size: 504

Participant exclusion criteria

Confirmed diagnosis of preterm pre-eclampsia at the point of enrolment

Recruitment start date

13/06/2016

Recruitment end date

27/10/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy’s and St Thomas’ NHS Foundation Trust
SE1 7EH

Trial participating centre

St George’s University Hospitals NHS Foundation Trust
SW17 0QT

Trial participating centre

Kingston Hospital NHS Foundation Trust
KT2 7QB

Trial participating centre

West Middlesex University Hospital
TW7 6AF

Trial participating centre

Central Manchester University Hospital NHS Foundation Trust
M13 9WL

Trial participating centre

Liverpool Women’s NHS Foundation Trust
L8 7SS

Trial participating centre

Leeds Teaching Hospitals NHS Trust
LS1 3EX

Trial participating centre

Bradford Teaching Hospitals NHS Foundation Trust
BD9 6RJ

Trial participating centre

Royal United Hospitals Bath
BA1 3NG

Trial participating centre

North Bristol NHS Trust
BS10 5NB

Trial participating centre

University Hospitals Bristol NHS Foundation Trust
BS2 8HW

Sponsor information

Organisation

Guy's and St Thomas' NHS Foundation Trust (UK)

Sponsor details

Westminster Bridge Road
London
SE1 9RT
United Kingdom
+44 (0)207 188 7188
lucy.chappell@kcl.ac.uk

Sponsor type

Hospital/treatment centre

Website

Organisation

King's College London (UK)

Sponsor details

Faculty of Life Sciences & Medicine
London
SE1 7EH
United Kingdom
+44 (0)20 7188 9853
lucy.chappell@kcl.ac.uk

Sponsor type

University/education

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

Not provided at time of registration

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

29/06/2016: Plain English summary added.