Condition category
Pregnancy and Childbirth
Date applied
20/11/2013
Date assigned
25/11/2013
Last edited
05/10/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Pre-eclampsia during pregnancy can be a very serious condition for both mother and baby. It can cause a sudden, rapid rise in blood pressure and cause seizures, strokes, multiple organ failure and on rare occasions, death. Babies whose mothers have pre-eclampsia tend to be smaller and more likely to be born prematurely or stillborn. The cause of pre-eclampsia is not known but it goes once a woman has given birth. The current guidelines state that women with pre-eclampsia should be hospitalized for careful monitoring and their labour induced once they reach 37 weeks of pregnancy. At 37 weeks of pregnancy, babies are generally considered to be fully developed (although most pregnancies go on to 40 weeks). Some doctors think, given that the complications of pre-eclampsia can be serious, that it would be better to induce labour before 37 weeks of pregnancy. The aim of this study is to find out whether inducing delivery earlier, when a woman is between 34 and 37 weeks of pregnancy, reduces the harm the condition can cause to the mother and baby despite the baby being born before they are considered to be fully developed.

Who can participate?
Women aged 18 or over who are between 34 and 37 weeks of pregnancy being cared for in a consultant-led maternity unit with confirmed pre-eclampsia but whose condition does not warrant immediate delivery are eligible to participate in the study. Women who are expecting twins are eligible if their twins have separate placentas and are being carried in separate membranes.

What does the study involve?
Women are randomly allocated to either the Planned Delivery Group or the Expectant Management Group. At this point, women are given a questionnaire to complete which gathers information on their health before they give birth. Women allocated to the Planned Delivery Group are induced within 48 hours of being allocated to the group. Generally, women are given a hormone called prostaglandin as a vaginal gel/pessary to start their labour. If this does not work, other methods of inducing labour are tried following the hospital’'s standard procedures. Before delivery is induced, doctors may want to give a steroid injection to the mother to help her baby’'s lungs mature faster. Women allocated to the Expectant Management Group continue to be closely monitored in hospital until they reach 37 weeks of pregnancy. At this time (or shortly afterwards), their labour is induced in the same way as for women in the Planned Delivery Group. However, if their health or that of their baby worsens, they may be delivered before this time. After delivery, women and their babies are cared for according to the hospital’'s standard practice regardless of the group they were allocated to. Information is collected on the health of the mother and baby until they are discharged from hospital. Six months after giving birth, women are sent a similar questionnaire to the one they completed whilst in hospital but the questionnaire also captures information on the NHS services that they have used since they were discharged. The questionnaire is again sent when their child reaches 2 years of age based on their due date. At this time a questionnaire is also sent to assess the health of their child.

What are the possible benefits and risks of participating?
It is difficult to separate the risks from the benefits of taking part in the study because they may balance each other out.
Women who are selected to be in the Planned Delivery Group may have their baby delivered up to 3 weeks (at 34 weeks of pregnancy) before they are usually fully developed (a baby is considered to be fully developed at 37 weeks but most pregnancies go on to 40 weeks). This may result in the baby having problems associated with being born early. However, letting the woman'’s pregnancy continue might harm them and their baby more. Women who are selected to be in the Expectant Management Group may become ill from the conditions associated with pre-eclampsia because their pregnancy is allowed to continue for longer. Also, their condition or that of their baby’s may suddenly worsen so that they have to be delivered quickly, which might be distressing. It is not yet known which of the two management strategies is the best and the aim of the study is to find this out.

Where is the study run from?
The study will be run initially from six hospitals with neonatal units to find out if the recruitment targets for the study can be met. It will then be opened up to approximately 34 more hospitals (40 in total).

When is the study starting and how long is it expected to run for?
April 2014 to August 2017

Who is funding the study?
National Institute for Healthcare Research (NIHR) (UK)

Who is the main contact?
Professor Andrew Shennan (andrew.shennan@kcl.ac.uk)
Dr Lucy Chappell, King’'s College London

Trial website

Contact information

Type

Scientific

Primary contact

Prof Andrew Shennan

ORCID ID

Contact details

Division of Women's Health
10th Floor
North Wing
St. Thomas' Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
+44 (0)20 7188 3639
andrew.shennan@kcl.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 12/25/03; HTA 15/59/06; EME 15/23/02

Study information

Scientific title

Pre-eclampsia in Hospital: Early Induction or Expectant Management

Acronym

PHOENIX

Study hypothesis

Study hypothesis: To determine whether planned delivery between 34+0 and 36+6 weeks of gestation in women with pre-clampsia reduces adverse maternal outcomes without substantially increasing neonatal/infant outcomes compared to the current recommended practice of expectant management and delivery at 37 weeks of gestation.

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/122503
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0010/98767/PRO-12-25-03.pdf

Added 05/10/2016:

PEACOCK (PHOENIX-2) sub-study: Prognostic indicators of severe disEAse in women with late preterm pre-eClampsia to guide deCision maKing on timing of delivery

Study hypothesis: To establish a prognostic model to inform optimal timing of delivery in women with late preterm pre-eclampsia, by comparing novel candidate biomarkers (e.g. plasma placental growth factor (PlGF)), with clinical and routinely collected blood/urinary markers to determine clinically indicated need for delivery within seven days of assessment.

Overall trial start date: 01/02/2016
Overall trial end date: 30/04/2018
Target number of participants: 600
Recruitment start date: 01/04/2016
Recruitment end date: 30/04/2018

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/155906

PHOEBE (PHOENIX-3) sub-study: Mechanisms of action of intervention in the PHOENIX trial: in women with preterm pre-eclampsia does planned delivery improve postpartum maternal cardiac function through attenuation of myocardial ischaemia at time of disease?

Study hypothesis: To examine the effects of delivery in women with late preterm preeclampsia, compared to expectant management and delivery at 37 weeks gestation on cardiovascular function at six months postpartum.

Overall trial start date: 01/02/2016
Overall trial end date: 30/04/2018
Target number of participants: 404
Recruitment start date: 01/04/2016
Recruitment end date: 30/04/2018

More details can be found at: http://www.nets.nihr.ac.uk/projects/eme/152302

Ethics approval

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Pre-eclampsia in women between 34+0 and 36+6 weeks of gestation

Intervention

Planned immediate delivery of women with pre-eclampsia between 34+0 and 36+6 weeks of gestation versus expectant management and delivery at 37 weeks of gestation.

Women will be followed up to until their child is 2 years of age, corrected for prematurity. If a woman is enrolled at 34 weeks of gestation (the earliest time point at which they can be enrolled), the total duration of her participation in the study will be 28 months.

Added 05/10/2016:

PEACOCK (PHOENIX-2) sub-study:
Clinical, blood and urine parameters taken at the time of randomisation into the PHOENIX trial in women with late preterm pre-eclampsia.

PHOEBE (PHOENIX-3) sub-study:
Non-revealed blood test for biomarker assessment of myocardial ischaemia (e.g. for highly sensitive cardiac troponin and Cardiac Myosin Binding Protein C), together with repeat non-revealed blood test and echocardiography with tissue Doppler studies at around 6 months postpartum.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Primary short-term maternal outcome:
Composite of maternal morbidity of fullPIERS (Pre-eclampsia Integrated Estimate of RiSk) outcomes with the addition of recorded systolic blood pressure >160 mmHg post randomisation.

Primary short-term perinatal outcome:
Composite of perinatal deaths (antenatal/intrapartum stillbirths and deaths within 7 days of delivery but not deaths due to congenital anomalies) and admissions to infant discharge.

Primary long-term infant outcome:
Neurodevelopmental assessment at 2 years of age (age corrected for prematurity) using PARCA-R Parent Report Composite.

Added 05/10/2016:

PEACOCK (PHOENIX-2) sub-study:
Primary short-term maternal outcome:
Clinically indicated need for delivery for pre-eclampsia (or related complications) within 7 days of assessment.

PHOEBE (PHOENIX-3) sub-study:
Primary long-term maternal outcome:
Composite of diastolic and systolic function classified according to the American College of Cardiology as assessed by echocardiography with tissue Doppler studies at 6 months postpartum.

Secondary outcome measures

Secondary short-term maternal outcomes:
Individual components of the composite primary outcome plus
1. Use of anti-hypertensive drugs
2. Progression to severe pre-eclampsia post-randomisation (defined as systolic blood pressure ≥ 160 mmHg, platelet count <100 x 109/litre, abnormal liver enzymes [ALT or AST >70 iu/litre])
3. Estimated fetal weight (on ultrasound scan) <10th centile post-enrolment
4. Absent or reversed end diastolic flow (on umbilical artery Doppler)
5. Time and mode of onset (spontaneous, induced or pre-labour caesarean section) and mode of delivery (spontaneous vaginal delivery, assisted vaginal delivery, caesarean section)
6. Confirmed thromboembolic disease requiring anticoagulation up to hospital discharge
7. Confirmed sepsis (positive blood or urine cultures) up to hospital discharge
8. Primary and additional indications for delivery in expectant management arm (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. Stillbirth post randomisation
2. Neonatal death prior to hospital discharge
3. Admission to Neonatal Unit (NNU)
4. Number of days in each category of care (intensive, high dependency, special, transitional and normal)
5. Total number of days in hospital
6. Birth weight (g)
7. Customised birth weight centile (GROW)
8. Birth weight <10th and <3rd customised centile
9. Gestational age at delivery
10. APGAR score at 5 minutes post birth
11. Umbilical arterial and venous pH (and base excess) at birth
12. Need for supplementary oxygen prior to discharge
13. Number of days when >2 hours of supplemental oxygen is required
14. Need for ventilation support (CPAP/high flow/endotracheal ventilation)
15. Abnormal cerebral ultrasound scan
16. Confirmed sepsis (positive blood or cerebrospinal fluid cultures)
17. Necrotising enterocolitis (Bell’s stage 2 and 3)
18. Seizures (confirmed by EEG and requiring anticonvulsant therapy)
19. Encephalopathy grade (worst at any time: mild, moderate, severe)
20. Hypoglycaemia (blood glucose <2.6 mmol/l on two or more occasions)
21. Other indications and main diagnoses resulting in NNU admission
22. Discharged home fully breast-fed

Secondary long-term maternal outcomes:
Maternal physical and mental health using the validated SF-12 questionnaire assessed at 6 months post delivery and 2 years (based on infant's age corrected for prematurity)

Health economic and quality of life outcomes:
1. Quality of life using the validated quality of life questionnaire EQ-5D immediately after randomisation, at 6 months and when the infant is 2 years of age corrected age for prematurity
2. Hospital attendances, nights and diagnostic tests from randomisation until delivery
3. Cost of delivery
4. Cost of neonatal care (hospital admissions, surgery and diagnostic tests)
5. Retrospective 6-month health/social care use by mother and infant at 6 months and 2 years
6. EQ-5D for the calculation of maternal quality-adjusted life-years (QALYs)

Added 05/10/2016:

PEACOCK (PHOENIX-2) sub-study:
1. Clinically indicated need for delivery for pre-eclampsia within 48 hours and within 14 days of assessment
2. Perinatal death
3. NNU admission

PHOEBE (PHOENIX-3) sub-study:
Diastolic blood pressure, systolic blood pressure, heart rate and cardiovascular components of the fullPIERS composite outcome (between enrolment and maternal discharge)

Overall trial start date

01/04/2014

Overall trial end date

31/08/2017

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 05/10/2016:
1. Women between 34+0 and 36+6 weeks of gestation
2. Confirmed as having pre-eclampsia (as defined as defined by International Society for the Study of Hypertension in Pregnancy {ISSHP} 2014 statement)
3. Singleton or dichorionic diamniotic (DCDA) twin pregnancy
4. Aged 18 years or over at the time of screening
5. Able to give written informed consent

Previous inclusion criteria:
1. Women between 34+0 and 36+6 weeks of gestation
2. Confirmed as having pre-eclampsia (as defined by the NICE guidelines on Hypertension in Pregnancy)
3. An in-patient in a consultant-led maternity unit
4. Singleton or dichorionic diamniotic (DCDA) twin pregnancy
5. Aged 18 years or over at the time of screening
6. Able to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

900

Participant exclusion criteria

Women will be excluded from participating in the study if a decision has already been made to delivery within the next 48 hours.

Recruitment start date

29/09/2014

Recruitment end date

31/08/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St. Thomas' Hospital
London
SE1 7EH
United Kingdom

Sponsor information

Organisation

King's College London (UK)

Sponsor details

King's College London
Strand
London
WC2R 2LS
United Kingdom
-
andrew.webb@kcl.ac.uk

Sponsor type

University/education

Website

http://www.kcl.ac.uk

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Funder name

Efficacy and Mechanism Evaluation Programme

Alternative name(s)

NIHR Efficacy and Mechanism Evaluation programme, EME

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

05/10/2016: Addition of two nested studies PEACOCK (PHOENIX-2) and PHOEBE (PHOENIX-3).