Clinical trial NCT02881073: Placental Growth Factor Assessment of Women With Suspected Pre-eclampsia
Official title: PARROT Ireland: Placental Growth Factor in Assessment of Women With Suspected Pre-eclampsia to Reduce Maternal Morbidity: a Randomised Control Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pre-eclampsia
Pregnancy, High Risk
Pregnancy Complications
Keywords: Placental Growth Factor
Maternal Morbidity
Neonatal Morbidity
Pre-eclampsia
Heath Economics
Lead sponsor: Irish Centre for Fetal and Neonatal Translational Research
Sponsor class: OTHER
Collaborators: name: National Maternity Hospital, Ireland
name: Rotunda Maternity Hospital, Dublin
name: Coombe Women and Infants University Hospital
name: University College Hospital Galway
name: Royal Jubilee Maternity Hospital, Belfast
name: Cork University Maternity Hospital
name: Univerisy Maternity Hospital, Limerick
name: University College Cork
First posted: 2016-08-26
Enrollment: 2313
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maternal Morbidity
timeFrame: up to 6 weeks post delivery
measure: Neonatal Morbidity
timeFrame: From neonates birth until time of discharge from the neonatal unit/hospital, up to 6 weeks post delivery
Secondary outcomes:
measure: Maternal Morbidity
timeFrame: up to 6 weeks post delivery
measure: Maternal Morbidity
timeFrame: up to 6 weeks post delivery
measure: Maternal Outcome-
timeFrame: up to 6 weeks post delivery
measure: Maternal Outcome
timeFrame: up to 6 weeks post delivery
measure: Maternal Outcome
timeFrame: up to 6 weeks post delivery
measure: Fetal Outcome
timeFrame: up to 6 weeks post delivery
measure: Fetal Outcome
timeFrame: up to 6 weeks post delivery
measure: Fetal Outcome
timeFrame: up to 6 weeks post delivery
measure: Heath Economic Outcomes
timeFrame: up to 6 weeks post delivery
measure: Heath Economic Outcomes
timeFrame: up to 6 weeks post delivery
measure: Fetal Quality of Life Assessment
timeFrame: up to 6 weeks post delivery
measure: Heath Economic Outcomes -Transport costs to patient of appointments
timeFrame: up to 6 weeks post delivery
measure: Maternal Quality of Life
timeFrame: 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
measure: Maternal Quality of Life
timeFrame: 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
Other outcomes:
Locations:
city: Belfast
country: Ireland
facility: Royal Jubilee Maternity Hospital
city: Cork
country: Ireland
facility: Cork University Maternity Hospital
city: Dublin
country: Ireland
facility: Coombe Womens & Infants University Hospital
city: Dublin
country: Ireland
facility: National Maternity Hospital
city: Dublin
country: Ireland
facility: Rotunda Maternity Hospital
city: Galway
country: Ireland
facility: University College Hospital Galway
city: Limerick
country: Ireland
facility: University Maternity Hospital Limerick
Study officials:
affiliation: Irish Centre for Fetal and Neonatal Translational Research
name: Louise C Kenny, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hayes-Ryan D, Khashan AS, Hemming K, Easter C, Devane D, Murphy DJ, Hunter A, Cotter A, McAuliffe FM, Morrison JJ, Breathnach FM, Dempsey E, Kenny LC, O'Donoghue K; PARROT Ireland trial group. Placental growth factor in assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a stepped wedge cluster randomised control trial (PARROT Ireland). BMJ. 2021 Aug 13;374:n1857. doi: 10.1136/bmj.n1857.
citation: Hayes-Ryan D, Meaney S, Nolan C, O'Donoghue K. An exploration of women's experience of taking part in a randomized controlled trial of a diagnostic test during pregnancy: A qualitative study. Health Expect. 2020 Feb;23(1):75-83. doi: 10.1111/hex.12969. Epub 2019 Oct 2.
citation: Hayes-Ryan D, Hemming K, Breathnach F, Cotter A, Devane D, Hunter A, McAuliffe FM, Morrison JJ, Murphy DJ, Khashan A, McElroy B, Murphy A, Dempsey E, O'Donoghue K, Kenny LC. PARROT Ireland: Placental growth factor in Assessment of women with suspected pre-eclampsia to reduce maternal morbidity: a Stepped Wedge Cluster Randomised Control Trial Research Study Protocol. BMJ Open. 2019 Mar 1;9(2):e023562. doi: 10.1136/bmjopen-2018-023562.