The Giant PANDA study: which blood pressure medication is best for pregnant women with high blood pressure?
| ISRCTN | ISRCTN12792616 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN12792616 |
| EudraCT/CTIS number | 2020-003410-12 |
| IRAS number | 284958 |
| Secondary identifying numbers | CPMS 47078, IRAS 284958 |
- Submission date
- 06/11/2020
- Registration date
- 18/11/2020
- Last edited
- 08/10/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Pregnancy and Childbirth
Plain English Summary
Background and study aims
Around 10% of women in the UK have high blood pressure in pregnancy, which without treatment can cause serious complications for the woman and baby. We want to find out which of the two most commonly used medicines to treat high blood pressure in pregnancy (labetalol and nifedipine) in the NHS is best at treating high blood pressure without having troublesome side effects for the woman or baby. Both medications have been widely used in the UK for many years and are considered safe in pregnancy.
The study aims to find out which blood pressure medication is best at treating high blood pressure in pregnancy.
Study results will help to understand which medication best treats high blood pressure in pregnancy and is safe for the baby, helping doctors and women with high blood pressure decide which medication is best for each woman and their baby.
Who can participate?
Pregnant women with hypertension, aged 18 years or over
What does the study involve?
Over 2,300 pregnant women with high blood pressure from around 50 maternity units in the UK that need treatment for their blood pressure will be offered information about the study and decide if they would like to take part. Women will be asked for their consent to take part and to complete a short questionnaire about how they are feeling. Women will then be randomly allocated (by chance) to either labetalol or nifedipine using a computer. To ensure women are treated safely, women and their healthcare team will know which medication group they are in. All women will continue to have their usual antenatal care including adding and switching their blood pressure medication and changing dose as needed. Two weeks after joining the study women will be asked to complete a few short questionnaires about how they are finding their blood pressure medication. Women and their babies will be followed through the pregnancy until they leave the hospital after birth.
What are the possible benefits and risks of participating?
Taking part will help us to understand how best to treat women with high blood pressure in pregnancy. Because women were about to be prescribed one of these two medications to treat their high blood pressure, there is very little risk to taking part. The only possible disadvantage is the additional time spent with the study team. We will keep these contacts as brief as possible, and if it is easier for women the two-week check-in can be over the phone or by email.
The doctor or healthcare professional prescribing their medication will explain any side effects as they usually would, and they can ask them at any time if they are not sure. The commonest side-effect reported for both drugs in pregnancy is a headache. Some women also reported dizziness or breathlessness. All women will continue to receive their usual NHS care during pregnancy while in this study.
Where is the study run from?
The Birmingham Clinical Trials Unit is running the study with Kings College London (UK)
When is the study starting and how long is it expected to run for?
April 2020 to September 2025
Who is funding the study?
National Institute for Health Research (NIHR) Health Technology Assessment Programme (UK)
Who is the main contact?
Lisa Leighton, Giant-PANDA@trials.bham.ac.uk
Contact information
Scientific
BCTU
Robert Aitken Institute
Birmingham University
Edgbaston
Birmingham
B15 2TT
United Kingdom
| Phone | +44 (0)121 415 9110 |
|---|---|
| Giant-PANDA@trials.bham.ac.uk |
Study information
| Study design | Randomized; Both; Design type: Treatment, Drug, Cohort study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | Pregnancy ANtihypertensive Drugs: which Agent is best? |
| Study acronym | Giant PANDA |
| Study hypothesis | Nifedipine will be superior compared to labetalol with less women in this group with severe systolic blood pressure readings, but the co-primary perinatal outcome will be no worse for the nifedipine group (non-inferior) compared with the labetalol group |
| Ethics approval(s) | Approved 03/11/2020, London - South East Research Ethics Committee (Barlow House, 3rd Floor, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)207 104 8085; londonsoutheast.rec@hra.nhs.uk), ref: 20/LO/1110 |
| Condition | Oedema, proteinuria and hypertensive disorders in pregnancy, childbirth and the puerperium |
| Intervention | The trial is a pragmatic, open-label, multicentre, two-arm randomised controlled trial of a treatment strategy with nifedipine versus labetalol in women with pregnancy hypertension. We aim to recruit 2,300 pregnant women (less than 34 weeks’ gestation), with pregnancy hypertension (chronic or gestational hypertension or pre-eclampsia), over 18 years, able to provide consent and where the decision has been made to initiate or continue use of anantihypertensive drug. Women will be identified by referral letters and/or at antenatal clinics and approached by a member of the direct clinical care team or the local research team (part of the direct care team) and provided with information on the study and given appropriate time to make the decision to participate. Following informed consent completion, women will be asked to complete a short questionnaire about how they feel. Women will then be randomised, by random allocation (1:1), to treatment with any preparation of modified release nifedipine, a calcium channel blocker, (intervention arm) or any preparation of labetalol, a mixed alpha/ beta blocker, (active control arm). Two weeks after randomisation women will be contacted by the research team and asked to complete a few short questionnaires about their blood pressure medication. Women and their babies will be in the study from consent until primary hospital discharge or 28 days post birth, whichever occurs sooner. This study is open-label to ensure women are effectively and safely treated, with healthcare professionals and women aware of their treatment allocation. Dose titration, switching, or add to the randomised antihypertensive drug will occur as in usual clinical practice as clinically indicated throughout pregnancy. If a woman declines randomisation to the trial then she will be offered participation in the Giant PANDA observational study, involving data collection only. All other aspects of antenatal and delivery care will follow usual clinical care pathways underpinned by NICE 2019 guidelines for pregnancy hypertension. The starting dose will be left to the discretion of the responsible healthcare professional, guided by blood pressure on the day, previous antihypertensive dose (where applicable) and any other relevant factors. The usual starting dose for the study drugs are: Labetalol - Oral - 100mg twice a day, increased to a maximum of 2,400mg total daily dose Nifedipine - Oral - 10mg twice a day, increased to a maximum of 40mg twice daily |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Labetalol, nifedipine |
| Primary outcome measure | 1. Maternal: Blood pressure measured using a sphygmomanometer daily between randomisation and birth 2. Fetal/neonatal: Composite of fetal loss before birth or known neonatal death, or neonatal unit admission between randomisation up to primary hospital discharge or 28 days post-birth, whichever occurs sooner (with no double counting of outcomes) |
| Secondary outcome measures | Measured using patient records: Up to birth: 1. Severe hypertension (defined as any episode of severe maternal hypertension (systolic blood pressure ≥160 mmHg between randomisation and birth)) 2. Mean antenatal systolic blood pressure (using highest systolic blood pressure per day as collected for the primary outcome) 3. New diagnosis of pre-eclampsia 4. Severe maternal morbidity (fullPIERS consensus definition (von Dadelszen, Payne et al. 2011)) 5. Discontinued allocated antihypertensive drug 6. Undesirable effects of allocated (and other) antihypertensive drug(s) (number of women and number of undesirable effects) At delivery/birth: 1. Indicated delivery (induction of labour or prelabour rupture of membranes (PROM) with stimulation of labour or pre-labour Caesarean section) Between birth and primary hospital discharge or 28 days post-birth, whichever occurs sooner: 1. Neonatal unit admission (separation of baby from mother) 2. Major congenital abnormality as defined by EUROCAT 3. Mode of birth (spontaneous vaginal, assisted vaginal, Caesarean section) 4. Gestational age at birth 5. Birthweight centile 6. Need for treatment for neonatal hypoglycaemia (in those having blood glucose monitoring) |
| Overall study start date | 01/04/2020 |
| Overall study end date | 30/09/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Female |
| Target number of participants | Planned Sample Size: 2,300; UK Sample Size: 2,300 |
| Participant inclusion criteria | 1. Pregnancy 11+0 and 34+6 weeks’ gestation inclusive 2. Diagnosis of pregnancy hypertension (chronic/gestational hypertension or pre-eclampsia) 3. Clinician decision to initiate or continue use of antihypertensive drugs 4. Aged 18 years or over 5. Able to give informed consent For observational study: 6. Women will be eligible to participate in the observational study at any gestational age up to and including 34+6 weeks. Women are able to take part in the observational study prior to 11+0 weeks gestation where the use of any antihypertensive drugs prescribed in clinical care will be recorded but will not form part of the interventional trial |
| Participant exclusion criteria | 1. Contraindication to either labetalol or nifedipine 2. Already taking both labetalol and nifedipine, and not able to be randomised to a single drug For observational study: 3. Neither exclusion criterion for the trial are relevant for the observational study. Women contraindicated to either labetalol or nifedipine and/or women already taking both labetalol and nifedipine and not able to be randomised to a single drug, are eligible for the observational study |
| Recruitment start date | 01/01/2021 |
| Recruitment end date | 31/12/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Oxford Road
Manchester
M13 9WL
United Kingdom
Crown Street
Liverpool
L8 7SS
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Birmingham
B4 6NH
United Kingdom
Derby Road
Nottingham
NG7 2UH
United Kingdom
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Duckworth Lane
Bradford
BD9 6RJ
United Kingdom
Bath
BA1 3NG
United Kingdom
Turner Road
Colchester
CO4 5JL
United Kingdom
Wolverhampton Road
Wolverhampton
WV10 0QP
United Kingdom
London
SW10 9NH
United Kingdom
Kingston upon Thames
KT2 7QB
United Kingdom
Blackshaw Road
Tooting
London
ST17 0QT
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
London
E9 6SR
United Kingdom
Sponsor information
University/education
Aston Webb building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)121 415 8011 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.birmingham.ac.uk/index.aspx |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Government
No information available
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/09/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Requests for the final dataset can be made through the chief investigator in accordance with the data-sharing policies of King’s College London and Birmingham Clinical Trials Unit, with input from the co-investigator group where applicable. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 12/09/2023 | 14/09/2023 | Yes | No | |
| Protocol file | version 1.2 | 18/08/2023 | 25/04/2024 | No | No |
| Statistical Analysis Plan | version 1.0 | 25/04/2024 | No | No | |
| Other publications | Inclusion of people with multiple long-term conditions in pregnancy research: patient, public and stakeholder involvement and engagement in a randomised controlled trial | 07/10/2024 | 08/10/2024 | Yes | No |
Additional files
Editorial Notes
08/10/2024: Publication reference added.
03/07/2024: The recruitment end date was changed from 31/07/2024 to 31/12/2024.
25/04/2024: Protocol and statistical analysis plan added.
01/03/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/07/2023 to 31/07/2024.
2. The overall study end date was changed from 31/03/2024 to 30/09/2025.
3. The intention to publish date was changed from 31/03/2025 to 30/09/2026.
14/09/2023: Publication reference added.
07/12/2022: The recruitment end date was changed from 30/12/2022 to 31/07/2023.
06/11/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).
