When to induce labour to limit risk in pregnancy hypertension
| ISRCTN | ISRCTN77258279 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN77258279 |
| Secondary identifying numbers | 252294; HTA 16/167/123 |
- Submission date
- 01/11/2018
- Registration date
- 05/12/2018
- Last edited
- 30/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
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 years 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?
1. Guy's and St Thomas' NHS Foundation Trust (UK)
2. Leeds Teaching Hospitals NHS Trust (UK)
3. Liverpool Women’s Hospital (UK)
4. Birmingham Women’s Hospital (UK)
5. West Middlesex Hospital (UK)
6. Croydon University Hospital (UK)
7. Leicester Royal Infirmary (UK)
8. Nottingham City Hospital (UK)
9. Queen’s Medical Centre (UK)
10. Princess Anne Hospital (UK)
11. St Mary’s Hospital (UK)
12. Poole Hospital (UK)
13. Norfolk & Norwich University Hospital NHS Foundation Trust (UK)
14. York Hospital (UK)
15. Singleton Hospital (UK)
16. North West Anglia NHS Foundation Trust (UK)
17. Royal United Hospital, Bath (UK)
18. South Tees Hospitals NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
June 2018 to January 2024
Who is funding the study?
NIHR Health Technology Assessment Programme (UK)
Who is the main contact?
Katie Kirkham
will@trials.bham.ac.uk
Contact information
Scientific
Birmingham Clinical Trials Unit (BCTU)
Institute of Applied Health Research
Public Health Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)1214159109 |
|---|---|
| will@trials.bham.ac.uk |
Study information
| Study design | Open-label interventional multicentre non-blinded study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | https://www.birmingham.ac.uk/research/bctu/trials/womens/will/investigators/documentation |
| 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 |
| Study 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(s) | Approved 10/01/2019, London - Fulham Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, Tel: +44 (0)207 104 8021; Email: nrescommittee.london-fulham@nhs.net), REC ref: 18/LO/2033, Protocol number: 252294, IRAS project ID: 252294 |
| Condition | Chronic or gestational hypertension that develops by 37+6 weeks gestation |
| Intervention | Current interventions as of 07/07/2023: 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. Usual care at term until, 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 31/01/2023. Previous interventions: 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 |
| 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 study start date | 01/06/2018 |
| Overall study end date | 31/01/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | 1080 |
| Total final enrolment | 403 |
| 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 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 | 03/06/2019 |
| Recruitment end date | 30/04/2022 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Great Maze Pond
London
SE1 9RT
United Kingdom
LS9 7TF
United Kingdom
Liverpool
L8 7SS
United Kingdom
Birmingham
B15 2TG
United Kingdom
Isleworth
TW7 6AF
United Kingdom
Croydon
CR7 7YE
United Kingdom
Leicester
LE1 5WW
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Southampton
SO16 5YA
United Kingdom
Manchester
M13 9WL
United Kingdom
Poole
BH15 2BH
United Kingdom
Norwich
NR4 7UY
United Kingdom
York
YO31 8HE
United Kingdom
Sketty
Swansea
SA2 8QA
United Kingdom
Huntingdon
PE29 6NT
United Kingdom
Bretton Gate
Peterborough
PE3 9GZ
United Kingdom
Bath
BA1 3NG
United Kingdom
Marton Rd
Middlesbrough
TS4 3BW
United Kingdom
Sponsor information
University/education
Room 5.31, James Clerk Maxwell Building
57 Waterloo Road
London
SE1 8WA
England
United Kingdom
| Website | http://www.kcl.ac.uk/index.aspx |
|---|---|
"ROR" |
https://ror.org/0220mzb33 |
Hospital/treatment centre
R&D Department
16th Floor, Tower Wing
Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)20 7188 7188; Int: 54462 |
|---|---|
| R&D@gstt.nhs.uk | |
| Website | http://www.guysandstthomas.nhs.uk/Home.aspx |
|
"ROR" |
https://ror.org/00j161312 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/01/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 plan | The datasets generated during and/or analysed during the current study are/will be available upon request from Laura Magee (laura.a.magee@kcl.ac.uk), anonymised data will be shared at the end of the trial. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | Adaptations to trial during COVID pandemic | 21/10/2022 | 24/10/2022 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 03/04/2023 | 30/05/2024 | Yes | No |
Editorial Notes
30/05/2024: The following changes were made to the study record:
1. Study website, participant information sheet, publication reference and IPD sharing plan added.
2. Scotland added to the countries of recruitment.
07/07/2023: The intention to publish date was changed from 31/07/2023 to 31/01/2024. The interventions were updated. Total final enrolment added.
28/04/2023: Internal review.
24/10/2022: Publication reference added.
01/04/2022: The overall trial end date has been changed from 30/04/2022 to 31/01/2024 and the plain English summary has been updated accordingly.
21/09/2021: Internal review.
13/07/2020: The recruitment resumed.
12/06/2020: Contact details updated.
20/04/2020: Due to current public health guidance, recruitment for this study has been paused.
07/10/2019: Trial participating centre added.
16/09/2019: Trial participating centre added.
12/09/2019: Trial participating centres added.
29/08/2019: Trial participating centre added.
28/08/2019: Trial participating centres added.
02/08/2019: Trial participating centre added.
17/07/2019: Trial participating centres added.
18/06/2019: Trial participating centres added.
05/06/2019: The following changes were made to the trial record:
1. The recruitment start date was changed from 01/01/2019 to 03/06/2019.
2. Trial participating centre and ethics approval details added.
