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Placental Growth Factor Assessment of Women With Suspected Pre-eclampsia

Not Applicable
Completed
Conditions
Pregnancy Complications
Pre-eclampsia
Pregnancy, High Risk
Interventions
Other: Maternal plasma PlGF quantification
Registration Number
NCT02881073
Lead Sponsor
Irish Centre for Fetal and Neonatal Translational Research
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
2313
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Maternal plasma PlGF quantificationMaternal plasma PlGF quantificationWomen 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.
Primary Outcome Measures
NameTimeMethod
Maternal Morbidityup to 6 weeks post delivery

assessed using a composite outcome combining the modified fullPIERS model for pre-eclampsia with sustained systolic blood pressure ≥ 160 mmHg

Neonatal MorbidityFrom neonates birth until time of discharge from the neonatal unit/hospital, up to 6 weeks post delivery

assessed using a composite neonatal score

Secondary Outcome Measures
NameTimeMethod
Maternal Outcome-up to 6 weeks post delivery

Progression to severe pre-eclampsia as defined by ACOG

Heath Economic Outcomesup to 6 weeks post delivery

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

Heath Economic Outcomes -Transport costs to patient of appointmentsup to 6 weeks post delivery

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.

Maternal Outcomeup to 6 weeks post delivery

Elective delivery: induction of labour or Caesarean section

Maternal Quality of LifeAssessed 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

Assessed through SF-6D questionnaire

Maternal Morbidityup to 6 weeks post delivery

Maternal morbidity by fullPIERS model (without systolic hypertension)

Fetal Outcomeup to 6 weeks post delivery

Gestation at delivery

Fetal Quality of Life Assessmentup to 6 weeks post delivery

Use utility values / decrements scale for infants to estimate the cost effectiveness of the intervention

Trial Locations

Locations (7)

Coombe Womens & Infants University Hospital

🇮🇪

Dublin, Ireland

University College Hospital Galway

🇮🇪

Galway, Ireland

Royal Jubilee Maternity Hospital

🇮🇪

Belfast, Ireland

Cork University Maternity Hospital

🇮🇪

Cork, Ireland

National Maternity Hospital

🇮🇪

Dublin, Ireland

Rotunda Maternity Hospital

🇮🇪

Dublin, Ireland

University Maternity Hospital Limerick

🇮🇪

Limerick, Ireland

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