Pre-eclampsiaPARROTNCT02881073
Placental Growth Factor Assessment of Women With Suspected Pre-eclampsia
A study testing Maternal plasma PlGF quantification in people with Pre-eclampsia and Pregnancy, High Risk, run by Irish Centre for Fetal and Neonatal Translational Research at 7 sites in Ireland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Pre-eclampsia, Pregnancy, High Risk, Pregnancy Complications
- What is being tested?
- Maternal plasma PlGF quantification
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,313 participants
- Where
- 7 sitesIreland
- Study dates
- 29 Jun 2017to 26 Apr 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- dipstick proteinuria
- suspected fetal growth restriction
- if the healthcare provider deems that the woman requires evaluation for possible pre-eclampsia
Who cannot join
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Ireland7 sites
Royal Jubilee Maternity Hospital
Belfast
Cork University Maternity Hospital
Cork
Coombe Womens & Infants University Hospital
Dublin
National Maternity Hospital
Dublin
Rotunda Maternity Hospital
Dublin
University College Hospital Galway
Galway
University Maternity Hospital Limerick
Limerick
About this study
Official title: PARROT Ireland: Placental Growth Factor in Assessment of Women With Suspected Pre-eclampsia to Reduce Maternal Morbidity: a Randomised Control Trial
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
Read the 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.
- Conditions
- Pre-eclampsia, Pregnancy, High Risk, Pregnancy Complications
- Being tested
- Maternal plasma PlGF quantification
- Keywords
- Placental Growth Factor, Maternal Morbidity, Neonatal Morbidity, Pre-eclampsia, Heath Economics
- Medical subject headings
- Pre-Eclampsia, Pregnancy Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Maternal plasma PlGF quantificationOther
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
| Study group | Role | What they receive |
|---|---|---|
| Control | No intervention | 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. |
| Maternal plasma PlGF quantification | Active comparator | 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. Receives: Other: Maternal plasma PlGF quantification |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maternal Morbidity
assessed using a composite outcome combining the modified fullPIERS model for pre-eclampsia with sustained systolic blood pressure ≥ 160 mmHg
Measured: up to 6 weeks post delivery
Neonatal Morbidity
assessed using a composite neonatal score
Measured: From neonates birth until time of discharge from the neonatal unit/hospital, up to 6 weeks post delivery
Secondary outcomes (14)
Maternal Morbidity
Final diagnosis of hypertensive disorder of pregnancy
Measured: up to 6 weeks post delivery
Maternal Morbidity
Maternal morbidity by fullPIERS model (without systolic hypertension)
Measured: up to 6 weeks post delivery
Maternal Outcome-
Progression to severe pre-eclampsia as defined by ACOG
Measured: up to 6 weeks post delivery
Maternal Outcome
Caesarean section: emergency or elective
Measured: up to 6 weeks post delivery
Maternal Outcome
Elective delivery: induction of labour or Caesarean section
Measured: up to 6 weeks post delivery
Fetal Outcome
Gestation at diagnosis of pre-eclampsia
Measured: up to 6 weeks post delivery
Fetal Outcome
Fetal growth restriction identified on antenatal ultrasound
Measured: up to 6 weeks post delivery
Fetal Outcome
Gestation at delivery
Measured: up to 6 weeks post delivery
Heath Economic Outcomes
Costs to Health Service of Community Based care: assessed through chart review at discharge
Measured: 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
Measured: 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
Measured: 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.
Measured: up to 6 weeks post delivery
Maternal Quality of Life
Assessed through EQ-5D-5L questionnaire
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2016 (estimated)
- Study start29 Jun 2017
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pre-eclampsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 2,313 participants (actual)
Sponsor and investigators
- Lead sponsor
- Irish Centre for Fetal and Neonatal Translational Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Maternity Hospital, Ireland, Rotunda Maternity Hospital, Dublin, Coombe Women and Infants University Hospital, University College Hospital Galway, Royal Jubilee Maternity Hospital, Belfast, Cork University Maternity Hospital, University Maternity Hospital Limerick, University College Cork
- Responsible party
- Sponsor
- Investigators
- Louise C Kenny, PhD, MD, Principal investigator, Irish Centre for Fetal and Neonatal Translational Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02881073
- Sponsor's protocol ID
- LK001-16
- Acronym
- PARROT
- Status last verified
- Aug 2019
- First submitted
- 10 Aug 2016
- Last updated
- 7 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34389547Hayes-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.
PubMed 31578808Hayes-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.
PubMed 30826791
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PARROT Ireland: Placental Growth Factor in Assessment of Women With Suspected Pre-eclampsia to Reduce Maternal Morbidity: a Randomised Control Trial
- ClinicalTrials.gov ID
- NCT02881073
- Acronym / sponsor ID
- PARROT / LK001-16
- Conditions
- Pre-eclampsia, Pregnancy, High Risk, Pregnancy Complications
- Keywords
- Placental Growth Factor, Maternal Morbidity, Neonatal Morbidity, Pre-eclampsia, Heath Economics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,313 participants (actual)
- Lead sponsor
- Irish Centre for Fetal and Neonatal Translational ResearchUniversity, hospital or other
- Collaborators
- National Maternity Hospital, Ireland, Rotunda Maternity Hospital, Dublin, Coombe Women and Infants University Hospital, University College Hospital Galway, Royal Jubilee Maternity Hospital, Belfast, Cork University Maternity Hospital, University Maternity Hospital Limerick, University College Cork
- Study start
- 29 Jun 2017 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 26 Aug 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | No intervention | –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. |
| Maternal plasma PlGF quantification | Active comparator | Other: Maternal 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Maternal plasma PlGF quantificationA 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 | Other | Maternal plasma PlGF quantification |
Primary outcome
Maternal Morbidity
Time frame: up 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 Morbidity
Time frame: From neonates birth until time of discharge from the neonatal unit/hospital, up to 6 weeks post delivery
assessed using a composite neonatal score
14 secondary outcomes
Maternal Morbidity
Time frame: up to 6 weeks post delivery
Maternal Morbidity
Time frame: up to 6 weeks post delivery
Maternal Outcome-
Time frame: up to 6 weeks post delivery
Maternal Outcome
Time frame: up to 6 weeks post delivery
Maternal Outcome
Time frame: up to 6 weeks post delivery
Fetal Outcome
Time frame: up to 6 weeks post delivery
Fetal Outcome
Time frame: up to 6 weeks post delivery
Fetal Outcome
Time frame: up to 6 weeks post delivery
Heath Economic Outcomes
Time frame: up to 6 weeks post delivery
Heath Economic Outcomes
Time frame: up to 6 weeks post delivery
Fetal Quality of Life Assessment
Time frame: up to 6 weeks post delivery
Heath Economic Outcomes -Transport costs to patient of appointments
Time frame: up to 6 weeks post delivery
Maternal Quality of Life
Time frame: 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
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
- Derived from this study: PubMed 34389547Hayes-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.
- Derived from this study: PubMed 31578808Hayes-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.
- Derived from this study: PubMed 30826791Hayes-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.
- Individual participant dataSharing planned: No
Related trials for Pre-eclampsia
Recruiting
Exercise to Improve Heart and Metabolic Health After Childbirth in Women at High Risk for Preeclampsia
Postpartum Exercise, Cardiometabolic Health
RecruitingObservational study
Molecular Study of the Maternal-fetal Interface in Preeclampsia.
Preeclampsia
Active, not recruitingObservational study
The CoPenHagen PREeClampsia and cardIOvascUlar diSease Study
Pre-Eclampsia, Atherosclerosis
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Not yet recruitingPhase 2
Furosemide vs Placebo in Severe Preeclampsia Postpartum
Severe Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louise C Kenny, PhD, MD principal investigator
Irish Centre for Fetal and Neonatal Translational Research
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Maternal plasma PlGF quantification in people with Pre-eclampsia and Pregnancy, High Risk, run by Irish Centre for Fetal and Neonatal Translational Research at 7 sites in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maternal Morbidity (time frame: up to 6 weeks post delivery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02881073, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.