Condition category
Pregnancy and Childbirth
Date applied
06/11/2020
Date assigned
18/11/2020
Last edited
18/11/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

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 with 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 March 2024

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

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Lisa Leighton

ORCID ID

Contact details

BCTU
Robert Aitken Institute
Birmingham University
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 9110
Giant-PANDA@trials.bham.ac.uk

Additional identifiers

EudraCT number

2020-003410-12

ClinicalTrials.gov number

Nil known

Protocol/serial number

CPMS 47078, IRAS 284958

Study information

Scientific title

Pregnancy ANtihypertensive Drugs: which Agent is best?

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

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

Study design

Randomized; Both; Design type: Treatment, Drug, Cohort study

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

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

Phase

Not Applicable

Drug names

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 trial start date

01/04/2020

Overall trial end date

31/03/2024

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Female

Target number of participants

Planned Sample Size: 2,300; UK Sample Size: 2,300

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

30/12/2022

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St Thomas' Hospital
Guy's and St Thomas' NHS Foundation Trust Westminster Bridge Road
London
SE1 7EH
United Kingdom

Trial participating centre

Manchester University Hospitals NHS Foundation Trust
Cobbett House Oxford Road
Manchester
M13 9WL
United Kingdom

Trial participating centre

Liverpool Women’s Hospital
Liverpool Women's NHS Foundation Trust Crown Street
Liverpool
L8 7SS
United Kingdom

Trial participating centre

St James University Hospital
Leeds Teaching Hospitals NHS Trust Beckett Street
Leeds
LS9 7TF
United Kingdom

Trial participating centre

Leicester Royal Infirmary
University Hospitals of Leicester NHS Trust Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Birmingham Women's and Children's NHS Foundation Trust
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Trial participating centre

Queen's Medical Centre
Nottingham University Hospitals NHS Trust Derby Road
Nottingham
NG7 2UH
United Kingdom

Trial participating centre

Bristol Royal Infirmary
University Hospitals Bristol and Weston NHS Foudnation Trust Marlborough Street
Bristol
BS1 3NU
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Bradford Teaching Hospitals NHS Foundation Trust Duckworth Lane
Bradford
BD9 6RJ
United Kingdom

Trial participating centre

Royal United Hospital
Combe Park
Bath
BA1 3NG
United Kingdom

Trial participating centre

Colchester Dist General Hospital
East Suffolk and North Essex NHS Foundation Trust Turner Road
Colchester
CO4 5JL
United Kingdom

Trial participating centre

New Cross Hospital
Royal Wolverhampton NHS Trust Wolverhampton Road
Wolverhampton
WV10 0QP
United Kingdom

Trial participating centre

Chelsea and Westminster Hospital
369 Fulham Road
London
SW10 9NH
United Kingdom

Trial participating centre

Kingston Hospital NHS Foundation Trust
Galsworthy Road
Kingston upon Thames
KT2 7QB
United Kingdom

Trial participating centre

St George's Hospital
St George's University Hospitals NHS Foundation Trust Blackshaw Road Tooting
London
ST17 0QT
United Kingdom

Trial participating centre

John Radcliffe Hospital
Oxford University Hospitals NHS Foundation Trust Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Southampton General Hospital
University Hospital Southampton NHS Foundation Trust Tremona Road
Southampton
SO16 6YD
United Kingdom

Trial participating centre

Homerton University Hospital NHS Foundation Trust
Homerton Row
London
E9 6SR
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Aston Webb building
Edgbaston
Birmingham
B15 2TT
United Kingdom
+44 (0)121 415 8011
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

http://www.birmingham.ac.uk/index.aspx

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: NIHR128721

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

National Institute for Health Research (NIHR) (UK)

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal.

IPD sharing statement:
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.

Intention to publish date

31/03/2025

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

06/11/2020: Trial’s existence confirmed by National Institute for Health Research (NIHR).