Placental Growth Factor Assessment of Women With Suspected Pre-eclampsia

Study Overview
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Brief Summary
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The primary aim is to establish the effectiveness of plasma PlGF measurement in reducing maternal morbidity (with assessment of perinatal safety in parallel) in women presenting with suspected pre-eclampsia prior to 37 weeks' gestation. The long term aim is to demonstrate that knowledge of PlGF measurement enables appropriate stratification of the antenatal management of women presenting with suspected pre-eclampsia, such that those at highest risk receive greater surveillance with a decrease in maternal adverse outcomes, and those at lower risk can be managed without unnecessary admission and other interventions, such that the results would influence international clinical practice in antenatal patient healthcare

Detailed Description
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Pre-eclampsia (PET), a disease of late pregnancy characterised by hypertension and proteinuria, complicates 2-8% of pregnancies and is associated with significant maternal and neonatal morbidity and mortality. Many reports have highlighted the frequent substandard care, often attributed to clinicians not identifying the seriousness of clinical signs suggestive of the disease. Consequently, improvements in prediction of development of PET have the potential to vastly improve clinical outcomes and reduce costs. Placental Growth Factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family and represents a key regulator of angiogenic events in pathological conditions. PlGF exerts its biological function through the binding and activation of the receptor Flt-1. In PET, it is thought that endothelial dysfunction leads to an increased level of a circulating decoy receptor, known as soluble Flt-1, (sFlt-1), a soluble receptor for both VEGF-A and PlGF. In 2013, the INFANT team were part of an international group that published the first multicentre prospective study (PELICAN) evaluating the use of PlGF in women presenting with suspected PET, which reported high sensitivity (95-96%) and negative predictive value (95-98%) for low PlGF in determining need for delivery for confirmed PET within 14 days. This study suggests that PlGF testing presents a realistic and innovative adjunct to the management of women with suspected PET, especially those presenting preterm.

Official Title
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PARROT Ireland: Placental Growth Factor in Assessment of Women With Suspected Pre-eclampsia to Reduce Maternal Morbidity: a Randomised Control Trial

Conditions
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Pre-eclampsia, Pregnancy, High Risk, Pregnancy Complications

Intervention / Treatment
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* Other: Maternal plasma PlGF quantification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women between 20+0 and 36+6 weeks of gestation (inclusive) Singleton pregnancy Aged 18 years or over Able to give informed consent, presenting with any symptoms of suspected pre-eclampsia Headache visual disturbances epigastric or right upper quadrant pain increasing oedema hypertension dipstick proteinuria suspected fetal growth restriction if the healthcare provider deems that the woman requires evaluation for possible pre-eclampsia Exclusion Criteria: Confirmed pre-eclampsia at point of enrolment (sustained hypertension with systolic BP ≥ 140 or diastolic BP ≥ 90 on at least two occasions at least 4hrs apart) with significant quantified proteinuria (>300mg protein on 24hr collection, urine protein creatinine ratio >30mg/mmol or +3 Dipstick Proteinuria) >37 weeks gestation Abnormal PET bloods Multiple pregnancy at any time point Decision regarding delivery already made Lethal fetal abnormality Previous participation in PELICAN trial in a prior pregnancy Unable/unwilling to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Eligible women at participating centres prior to roll-out of PlGF testing (as per stepped wedge trial design) will be managed according to HSE/Institute of Obstetrician and Gynaecologists' National Guidelines for 'The management of hypertensive disorders during pregnancy' & The management of Pre-eclampsia or by NICE guidelines for Management of Hypertension in Pregnancy for those in Northern Ireland. | |
| Active Comparator: Maternal plasma PlGF quantification<br>Women in the interventional arm will have an additional point of care test performed at the time of enrolment for immediate PlGF quantification. The PlGF measurement will be reported as the absolute value in pg/ml with the following ranges given: PlGF <12 pg/ml: Very low PlGF ≥12 and <100 pg/ml: Low PlGF ≥100 pg/ml: Normal All hospitals will follow National Guidelines for 'The management of hypertensive disorders during pregnancy' & The management of Pre-eclampsia with the additional integration of PlGF results as indicated in the algorithm. | Other: Maternal plasma PlGF quantification<br>* A point of care test performed on maternal plasma, to quantify the level of the protein PlGF (placental growth factor) in the serum of the pregnant woman with suspected pre eclampsia to help the clinician in stratifying the level of further care for her in her pregnancy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal Morbidity | assessed using a composite outcome combining the modified fullPIERS model for pre-eclampsia with sustained systolic blood pressure ≥ 160 mmHg | up to 6 weeks post delivery | 
| Neonatal Morbidity | assessed using a composite neonatal score | From neonates birth until time of discharge from the neonatal unit/hospital, up to 6 weeks post delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal Morbidity | Final diagnosis of hypertensive disorder of pregnancy | up to 6 weeks post delivery | 
| Maternal Morbidity | Maternal morbidity by fullPIERS model (without systolic hypertension) | up to 6 weeks post delivery | 
| Maternal Outcome- | Progression to severe pre-eclampsia as defined by ACOG | up to 6 weeks post delivery | 
| Maternal Outcome | Caesarean section: emergency or elective | up to 6 weeks post delivery | 
| Maternal Outcome | Elective delivery: induction of labour or Caesarean section | up to 6 weeks post delivery | 
| Fetal Outcome | Gestation at diagnosis of pre-eclampsia | up to 6 weeks post delivery | 
| Fetal Outcome | Fetal growth restriction identified on antenatal ultrasound | up to 6 weeks post delivery | 
| Fetal Outcome | Gestation at delivery | up to 6 weeks post delivery | 
| Heath Economic Outcomes | Costs to Health Service of Community Based care: assessed through chart review at discharge | up to 6 weeks post delivery | 
| Heath Economic Outcomes | Costs to Health Service of inpatient/day case care: Assessed by chart review at discharge thought HIPE/HPO/Length of stay for both mother and baby | up to 6 weeks post delivery | 
| Fetal Quality of Life Assessment | Use utility values / decrements scale for infants to estimate the cost effectiveness of the intervention | up to 6 weeks post delivery | 
| Heath Economic Outcomes -Transport costs to patient of appointments | Identified through a costing questionnaire given to the patient to complete at discharge from hospital post delivery. Will ask how far patient lives from their GP and their hospital and their means of transport when attending appointments and thus calculate the transport cost to a patient throughout the pregnancy of attending their appointments. | up to 6 weeks post delivery | 
| Maternal Quality of Life | Assessed through EQ-5D-5L questionnaire | Assessed at two individual timepoints during the trial: once at time of enrolment to the study and repeated again post delivery and up to 6 weeks post delivery | 
| Maternal Quality of Life | Assessed through SF-6D questionnaire | Assessed at two individual timepoints during the trial: once at time of enrolment to the study and repeated again post delivery and up to 6 weeks post delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Placental Growth Factor, Maternal Morbidity, Neonatal Morbidity, Pre-eclampsia, Heath Economics