A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA)

Danielle Ashworth; Cheryl Battersby; Debra Bick; Marcus Green; Pollyanna Hardy; Lisa Leighton; Laura A. Magee; Alisha Maher; Richard J. McManus; Catherine Moakes; R. Katie Morris; Catherine Nelson-Piercy; Jenie Sparkes; Oliver Rivero-Arias; Andrew Webb; Hannah Wilson; Jenny Myers; Lucy C. Chappell

doi:10.1186/s13063-023-07582-9

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA)

Danielle Ashworth, Cheryl Battersby, Debra Bick, Marcus Green, Pollyanna Hardy, Lisa Leighton, Laura A. Magee, Alisha Maher, Richard J. McManus, Catherine Moakes, R. Katie Morris, Catherine Nelson-Piercy, Jenie Sparkes, Oliver Rivero-Arias, Andrew Webb, Hannah Wilson, Jenny Myers, Lucy C. Chappell^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Background: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration: EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

Original language	English
Article number	584
Journal	Trials
Volume	24
Issue number	1
Early online date	12 Sept 2023
DOIs	https://doi.org/10.1186/s13063-023-07582-9
Publication status	Published - Dec 2023

Keywords

Antihypertensives
Blood pressure
Hypertension
Pregnancy
Randomised controlled trial

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ashworth, D., Battersby, C., Bick, D., Green, M., Hardy, P., Leighton, L., Magee, L. A., Maher, A., McManus, R. J., Moakes, C., Morris, R. K., Nelson-Piercy, C., Sparkes, J., Rivero-Arias, O., Webb, A., Wilson, H., Myers, J., & Chappell, L. C. (2023). A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA). Trials, 24(1), Article 584. https://doi.org/10.1186/s13063-023-07582-9

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title = "A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA)",

abstract = "Background: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration: EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.",

keywords = "Antihypertensives, Blood pressure, Hypertension, Pregnancy, Randomised controlled trial",

author = "Danielle Ashworth and Cheryl Battersby and Debra Bick and Marcus Green and Pollyanna Hardy and Lisa Leighton and Magee, {Laura A.} and Alisha Maher and McManus, {Richard J.} and Catherine Moakes and Morris, {R. Katie} and Catherine Nelson-Piercy and Jenie Sparkes and Oliver Rivero-Arias and Andrew Webb and Hannah Wilson and Jenny Myers and Chappell, {Lucy C.}",

note = "Funding Information: The Giant Pregnancy ANtihypertensive Drugs: which Agent is best? (PANDA) https://fundingawards.nihr.ac.uk/award/NIHR128721 study aims to compare a treatment strategy of nifedipine versus labetalol in women with pregnancy hypertension. It addresses a research recommendation first published by NICE in 2010 and reiterated in the 2019 update []. Our study is also informed by the findings of a four-centre feasibility study (ISRCTN40973936) and developed by a multidisciplinary team with outcomes chosen by patient and public involvement. This study is funded by the National Institute for Health and Care Research Health Technology Assessment programme and has been approved by the Health Research Authority and Medicines and Healthcare products Regulatory Agency, together with NHS Trust Research and Development Offices for each site. Funding Information: This study is funded by the National Institute for Health and Care Research Health Technology Assessment programme and sponsored by the University of Birmingham. The study funder and sponsor will have no role in its execution, analyses, interpretation of the data, or decision to submit results. Funding Information: LCC is a chief scientific adviser for the Department of Health and Social Care (DHSC). RJM and LCC are NIHR senior investigators. CB is supported by an NIHR advanced fellowship. Publisher Copyright: {\textcopyright} 2023, BioMed Central Ltd., part of Springer Nature.",

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doi = "10.1186/s13063-023-07582-9",

language = "English",

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Ashworth, D, Battersby, C, Bick, D, Green, M, Hardy, P, Leighton, L, Magee, LA, Maher, A, McManus, RJ, Moakes, C, Morris, RK, Nelson-Piercy, C, Sparkes, J, Rivero-Arias, O, Webb, A, Wilson, H, Myers, J & Chappell, LC 2023, 'A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA)', Trials, vol. 24, no. 1, 584. https://doi.org/10.1186/s13063-023-07582-9

TY - JOUR

T1 - A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension

T2 - study protocol for a randomised controlled trial (Giant PANDA)

AU - Ashworth, Danielle

AU - Battersby, Cheryl

AU - Bick, Debra

AU - Green, Marcus

AU - Hardy, Pollyanna

AU - Leighton, Lisa

AU - Magee, Laura A.

AU - Maher, Alisha

AU - McManus, Richard J.

AU - Moakes, Catherine

AU - Morris, R. Katie

AU - Nelson-Piercy, Catherine

AU - Sparkes, Jenie

AU - Rivero-Arias, Oliver

AU - Webb, Andrew

AU - Wilson, Hannah

AU - Myers, Jenny

AU - Chappell, Lucy C.

N1 - Funding Information: The Giant Pregnancy ANtihypertensive Drugs: which Agent is best? (PANDA) https://fundingawards.nihr.ac.uk/award/NIHR128721 study aims to compare a treatment strategy of nifedipine versus labetalol in women with pregnancy hypertension. It addresses a research recommendation first published by NICE in 2010 and reiterated in the 2019 update []. Our study is also informed by the findings of a four-centre feasibility study (ISRCTN40973936) and developed by a multidisciplinary team with outcomes chosen by patient and public involvement. This study is funded by the National Institute for Health and Care Research Health Technology Assessment programme and has been approved by the Health Research Authority and Medicines and Healthcare products Regulatory Agency, together with NHS Trust Research and Development Offices for each site. Funding Information: This study is funded by the National Institute for Health and Care Research Health Technology Assessment programme and sponsored by the University of Birmingham. The study funder and sponsor will have no role in its execution, analyses, interpretation of the data, or decision to submit results. Funding Information: LCC is a chief scientific adviser for the Department of Health and Social Care (DHSC). RJM and LCC are NIHR senior investigators. CB is supported by an NIHR advanced fellowship. Publisher Copyright: © 2023, BioMed Central Ltd., part of Springer Nature.

PY - 2023/12

Y1 - 2023/12

N2 - Background: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration: EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

AB - Background: Approximately one in ten women have high blood pressure during pregnancy. Hypertension is associated with adverse maternal and perinatal outcomes, and as treatment improves maternal outcomes, antihypertensive treatment is recommended. Previous trials have been unable to provide a definitive answer on which antihypertensive treatment is associated with optimal maternal and neonatal outcomes and the need for robust evidence evaluating maternal and infant benefits and risks remains an important, unanswered question for research and clinical communities. Methods: The Giant PANDA study is a pragmatic, open-label, multicentre, randomised controlled trial of a treatment initiation strategy with nifedipine (calcium channel blocker), versus labetalol (mixed alpha/beta blocker) in 2300 women with pregnancy hypertension. The primary objective is to evaluate if treatment with nifedipine compared to labetalol in women with pregnancy hypertension reduces severe maternal hypertension without increasing fetal or neonatal death or neonatal unit admission. Subgroup analyses will be undertaken by hypertension type (chronic, gestational, pre-eclampsia), diabetes (yes, no), singleton (yes, no), self-reported ethnicity (Black, all other), and gestational age at randomisation categories (11 + 0 to 19 + 6, 20 + 0 to 27 + 6, 28 + 0 to 34 + 6 weeks). A cost-effectiveness analysis using an NHS perspective will be undertaken using a cost-consequence analysis up to postnatal hospital discharge and an extrapolation exercise with a lifetime horizon conditional on the results of the cost-consequence analysis. Discussion: This trial aims to address the uncertainty of which antihypertensive treatment is associated with optimal maternal and neonatal outcomes. The trial results are intended to provide definitive evidence to inform guidelines and linked, shared decision-making tools, thus influencing clinical practice. Trial registration: EudraCT number: 2020–003410-12, ISRCTN: 12,792,616 registered on 18 November 2020.

KW - Antihypertensives

KW - Blood pressure

KW - Hypertension

KW - Pregnancy

KW - Randomised controlled trial

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DO - 10.1186/s13063-023-07582-9

M3 - Article

C2 - 37700365

AN - SCOPUS:85170698118

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VL - 24

JO - Trials

JF - Trials

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ER -

A treatment strategy with nifedipine versus labetalol for women with pregnancy hypertension: study protocol for a randomised controlled trial (Giant PANDA)

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Keywords

UN SDGs

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