PlGF as a diagnostic test for pre-eclampsia

• Register: ISRCTN
• Last refreshed on: 5 May 2019
• Main ID: ISRCTN16842031
• Date of registration: 19/05/2016
• Prospective Registration: Yes
• Primary sponsor: Guy's and St Thomas' NHS Foundation Trust (UK)
• Public title: PlGF as a diagnostic test for pre-eclampsia
• Scientific title: PARROT - Placental growth factor to Assess and diagnose hypeRtensive pRegnant wOmen: a stepped wedge Trial
• Date of first enrolment: 13/06/2016
• Target sample size: 504
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN16842031
• Study type: Interventional
• Study design: Stepped-wedge designed multicentre randomised controlled trial (Prevention)
• Phase: Not Applicable

Countries of recruitment

United Kingdom

Contacts

• Name: Kate Duhig

Key inclusion & exclusion criteria

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

Exclusion criteria: Confirmed diagnosis of preterm pre-eclampsia at the point of enrolment

Age minimum:
Age maximum:
Gender: Both

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
Pregnancy and Childbirth
Pre-eclampsia

Intervention(s)

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.

Primary Outcome(s)

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(s)

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.

Secondary ID(s)

30737

Source(s) of Monetary Support

National Institute for Health Research

Secondary Sponsor(s)

King's College London (UK)

Ethics review

Status:
Approval date:
Contact:

South London Research Ethics Committee, 21/01/2016, ref: 15/LO/2058

Results

• Results available: Yes
• Date Completed: 31/03/2018