Condition category
Pregnancy and Childbirth
Date applied
01/11/2018
Date assigned
05/12/2018
Last edited
05/12/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
This study is looking to enrol pregnant women who have high blood pressure (hypertension) during their pregnancy. High blood pressure increases the risk of harm to the mother and to her baby, and the study is being conducted to see when it is best to deliver the baby in order to minimise this risk as much as possible. In the UK, up to 55,000 pregnant women each year have high blood pressure during their pregnancies. It is not known whether delivery should be started before the onset of spontaneous labour that usually occurs at term, defined as 37-42 weeks (within which is the ‘due date’ of 40 weeks of pregnancy). Early planned delivery at term (at 37-38 weeks) may reduce stillbirth and complications for the mother, such as separation of the placenta from the wall of the womb, or development of pre-eclampsia, a more concerning form of high blood pressure that is associated with protein in the urine or other problems for mothers and babies and possibly Caesarean delivery. However, early planned delivery at term may also cause harm, including newborn health problems such as breathing or other difficulties that may require the baby to need care in a newborn unit. This study is looking at the experiences of 1,080 pregnant women with hypertension who have been pregnant for at least 36 to 37 weeks to see if delivering their baby between 38 weeks plus zero days to 38 weeks plus 3 days gives a better outcome for the mother and her baby than does waiting for at least 40 weeks for the women to deliver. At the moment there is no conclusive evidence to say which delivery time is best. Different doctors do different things and this is why this study is needed.

Who can participate?
Women aged 16 and over who are 36 to 37 weeks pregnant and have hypertension

What does the study involve?
Participants are randomly allocated to planned birth at 38 weeks, or planned observation of pregnancy until at least 40 weeks (unless an indication for birth develops). The research midwife contacts participants weekly until the birth. Before leaving hospital after birth, participants are asked to complete a two-page questionnaire about their experience of childbirth. At 6 weeks after birth, they are sent a very brief online questionnaire via a text message, to find out about any serious problems that the mothers or babies may have experienced since leaving hospital after birth. There is support throughout from dedicated research midwives.

What are the possible benefits and risks of participating?
Mothers and babies are closely monitored. The knowledge gained from this research might in the future benefit many, many women with high blood pressure in pregnancy. The study involves no new interventions and has no added risks to the mother or baby; instead, the study measures risk.

Where is the study run from?
Guy's and St Thomas' NHS Foundation Trust (UK)

When is the study starting and how long is it expected to run for?
June 2018 to April 2022

Who is funding the study?
NIHR Health Technology Assessment Programme (UK)

Who is the main contact?
Mrs Kirandeep Sunner

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Kirandeep Sunner

ORCID ID

Contact details

Birmingham Clinical Trials Unit (BCTU)
Institute of Applied Health Research
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

252294; HTA 16/167/123

Study information

Scientific title

When to Induce Labour to Limit risk in pregnancy hypertension - a multi-centre, randomised controlled trial in women with chronic or gestational hypertension

Acronym

WILL

Study hypothesis

Earlier delivery at term may be beneficial to women with chronic or gestational hypertension, without increasing risk to babies or caesarean delivery.

The trial will investigate the clinical effectiveness and cost-consequences of planned early term delivery at 38+0 to 38+3 weeks gestation, compared with expectant care at term until at least 40+0 weeks gestation.

Ethics approval

Approval pending

Study design

Open-label interventional multicentre non-blinded study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Condition

Chronic or gestational hypertension that develops by 37+6 weeks gestation

Intervention

Randomisation will be provided through a bespoke database provided by BCTU.

1. Planned early term delivery at 38+0 to 38+3 weeks by labour induction (local protocol) or elective Caesarean (if previously indicated)
2. Expectant care at term until at least 40+0 weeks, with maternal and fetal monitoring (local protocol), awaiting spontaneous labour or delivery indicated by clinical need (e.g., refractory severe hypertension or pre-eclampsia)

Follow up: 31/11/2018 to 20/04/2022.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

1. Maternal co-primary outcome: Composite of poor maternal outcome until primary hospital discharge home or 28 days after delivery birth (whichever is earlier), defined as:
1.1. Severe hypertension (i.e., systolic BP (sBP) ≥160 or diastolic BP ≥110mmHg); or
1.2. Maternal death; or
1.3. Maternal morbidity defined as any of the following: GCS<13; stroke; TIA; eclampsia; blindness; uncontrolled hypertension; inotropic support; pulmonary oedema; respiratory failure; SpO2 <90%; myocardial ischaemia or infarction; hepatic dysfunction, hepatic haematoma or rupture; acute kidney injury or dialysis; platelet count <50x109/L; transfusion; or placental abruption. These were adapted from a Delphi consensus in hypertensive pregnancy.
Measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
2. Neonatal co-primary outcome: Neonatal care unit admission for ≥ 4 hours, measured by review of maternity or neonatal notes/electronic records until primary hospital discharge home or 28 days after delivery birth (whichever is earlier)

Secondary outcome measures

Maternal:
1. Caesarean delivery, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
2. Instrumental vaginal delivery or Caesarean delivery (vs. spontaneous vaginal delivery), measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
3. Individual components of maternal co-primary outcome, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
4. Elevated liver enzymes, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
5. Platelet count <100x109/L, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
6. Pre-eclampsia, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
7. Sepsis, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
8. Postpartum haemorrhage (PPH), measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
9. Intensive care unit (ITU) admission, measured by review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)

Potential co-interventions (only among women randomised):
1. Antihypertensive therapy taken, measured using review of maternity notes/electronic records ntil uprimary hospital discharge home or 28 days after birth (whichever is earlier)
2. Magnesium sulphate, measured using review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
3. Bedrest at home, measured using review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
4. Use of home BP monitoring, measured using review of maternity notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
5. Maternal blood/urine testing at lab before delivery admission, measured using review of maternity notes/electronic records after randomisation before birth
6. Office/clinic visits, measured using review of maternity notes/electronic records after randomisation before birth
7. Obstetrical day unit visits, measured using review of maternity notes/electronic records after randomisation before birth
8. Acute care visits, measured using review of maternity notes/electronic records after randomisation before birth
9. Antenatal admissions, measured using review of maternity notes/electronic records after randomisation before birth
10. Fetal cardiotocography, measured using review of maternity notes/electronic records after randomisation before birth
11. Fetal ultrasound, measured using review of maternity notes/electronic records after randomisation before birth

1. Clinical indications for delivery in the expectant care arm, measured using review of maternity notes/electronic records after randomisation before birth
2. Maternal satisfaction, measured using Childbirth Experience Questionnaire 2.0 until primary hospital discharge home or 28 days after birth (whichever is earlier)
3. ‘Poor maternal outcome’‡, measured using review of maternity notes/electronic records and postpartum questionnaire at 6 weeks after birth
4. Infection of the Caesarean wound, episiotomy or vaginal tear, as applicable‡, measured using postpartum questionnaire at 6 weeks after birth

Neonatal:
1. Neonatal care unit admission, measured using review of maternity or neonatal notes/electronic records and 6 week postpartum questionnaire until 28 days after birth
2. Indication for neonatal care unit admission ≥ 4 hours, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
3. Respiratory morbidity, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
4. Hypoxic-ischaemic encephalopathy (HIE), measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
5. Sepsis, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
6. Major operation, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
7. Intra-uterine fetal death, assessed by ultrasound doppler antepartum and lack of vital signs at birth
8. Neonatal death, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
9. Breastfeeding established, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)
10. Exclusive breastfeeding, measured using review of neonatal notes/electronic records until primary hospital discharge home or 28 days after birth (whichever is earlier)

Health Economics
Cost-consequence analysis from NHS perspective, measured using review of neonatal notes/electronic records for individual-level data until primary hospital discharge home or 28 days after birth (whichever is earlier)

‡ Only among women randomised

Overall trial start date

01/06/2018

Overall trial end date

30/04/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Maternal age ≥16 years
2. Diagnosis of chronic or gestational hypertension
3. Singleton pregnancy
4. Live fetus
5. Gestational age of 36+0 to 37+6 weeks
6. Able to give written informed consent to participate

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

1080

Participant exclusion criteria

1. Contraindication to either one of the trial arms (e.g., evidence of pre-eclampsia)
2. Severe hypertension [i.e., blood pressure (BP) ≥160mmHg systolic or ≥110mmHg diastolic] until BP falls below this level (i.e. it is ‘controlled’)
3. Major fetal anomaly anticipated to require neonatal unit admission
4. Participation in another timing of delivery trial
NOTE: Women with co-morbidities (e.g., diabetes) and fetal size will not be exclusion criteria

Recruitment start date

01/01/2019

Recruitment end date

30/04/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
R&D Department 16th Floor, Tower Wing Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor information

Organisation

King’s College London

Sponsor details

Room 5.31
James Clerk Maxwell Building
57 Waterloo Road
London
SE1 8WA
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Organisation

Guy's & St Thomas' Foundation NHS Trust

Sponsor details

R&D Department
16th Floor
Tower Wing
Great Maze Pond
London
SE1 9RT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

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

Results and Publications

Publication and dissemination plan

Results of this trial will be submitted for publication in peer-reviewed journals. The manuscript will be prepared by the TMG; all contributors to the trial will be listed, with their contribution identified and specifically, all collaborating site teams will be listed in an Appendix as the ‘WILL Study Group’. Abstracts will be submitted to international medical congresses. Trial participants will be able to access the final results of the trial via the trial website. All publications/presentations that use data from this trial to undertake original analyses will be submitted to the Funders for review before release; these must be submitted in a timely fashion and in advance of being submitted for publication, to allow time for review and resolution of any outstanding issues.
On all publications, the authors must acknowledge that the trial was: (i) performed with the support of The UofB BCTU, King’s College London, and Guy’s and St. Thomas’ Foundation NHS Trust; and (ii) funded by the NIHR. To safeguard the scientific integrity of the trial, data from this trial will not be presented in public

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/07/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes