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
Study website
Additional identifiers
EudraCT/CTIS number
IRAS 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(s)
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
Study setting(s)
Hospital
Study 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
Primary outcome measure
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
Current secondary outcome measures as of 08/06/2018:
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)
7. A composite of maternal adverse outcomes as defined by the fullPIERS consensus
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.
Previous 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 study start date
01/04/2016
Overall study end date
31/03/2018
Reason abandoned (if study stopped)
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(s)
Patient
Age group
Adult
Lower age limit
18 Years
Sex
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
England, United Kingdom
Study participating centre
Guy’s and St Thomas’ NHS Foundation Trust
SE1 7EH
United Kingdom
Study participating centre
St George’s University Hospitals NHS Foundation Trust
SW17 0QT
United Kingdom
Study participating centre
Kingston Hospital NHS Foundation Trust
KT2 7QB
United Kingdom
Study participating centre
West Middlesex University Hospital
TW7 6AF
United Kingdom
Study participating centre
Central Manchester University Hospital NHS Foundation Trust
M13 9WL
United Kingdom
Study participating centre
Liverpool Women’s NHS Foundation Trust
L8 7SS
United Kingdom
Study participating centre
Leeds Teaching Hospitals NHS Trust
LS1 3EX
United Kingdom
Study participating centre
Bradford Teaching Hospitals NHS Foundation Trust
BD9 6RJ
United Kingdom
Study participating centre
Royal United Hospitals Bath
BA1 3NG
United Kingdom
Study participating centre
North Bristol NHS Trust
BS10 5NB
United Kingdom
Study participating centre
University Hospitals Bristol NHS Foundation Trust
BS2 8HW
United Kingdom
Sponsor information
Organisation
Guy's and St Thomas' NHS Foundation Trust (UK)
Sponsor details
Westminster Bridge Road
London
SE1 9RT
England
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
England
United Kingdom
+44 (0)20 7188 9853
lucy.chappell@kcl.ac.uk
Sponsor type
University/education
Website
Organisation
Guy's and St Thomas' NHS Foundation Trust
Sponsor details
Sponsor type
Not defined
Website
http://www.guysandstthomas.nhs.uk/Home.aspx
ROR
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
31/03/2019
Individual participant data (IPD) sharing plan
IPD sharing plan summary
Available on request
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 04/05/2019 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |