PlGF as a diagnostic test for pre-eclampsia
| ISRCTN | ISRCTN16842031 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16842031 |
| Secondary identifying numbers | 30737 |
- Submission date
- 18/05/2016
- Registration date
- 19/05/2016
- Last edited
- 08/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
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
Contact information
Public
Womens Health
St Thomas' Hospital
London
SE1 7EH
United Kingdom
Study information
| 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 |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | PARROT - Placental growth factor to Assess and diagnose hypeRtensive pRegnant wOmen: a stepped wedge Trial |
| Study acronym | PARROT |
| Study objectives | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Completion date | 31/03/2018 |
Eligibility
| 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 |
| Key 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 |
| Key exclusion criteria | Confirmed diagnosis of preterm pre-eclampsia at the point of enrolment |
| Date of first enrolment | 13/06/2016 |
| Date of final enrolment | 27/10/2017 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
Sponsor information
Hospital/treatment centre
Westminster Bridge Road
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)207 188 7188 |
|---|---|
| lucy.chappell@kcl.ac.uk |
University/education
Faculty of Life Sciences & Medicine
London
SE1 7EH
England
United Kingdom
| Phone | +44 (0)20 7188 9853 |
|---|---|
| lucy.chappell@kcl.ac.uk |
Not defined
Funders
Funder type
Government
Government organisation / National government
- 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
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/03/2019 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
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 |
Editorial Notes
08/04/2019: Publication reference added.
08/06/2018: The secondary outcome measures have been changed.
23/10/2017: Internal review.
29/06/2016: Plain English summary added.
