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
Affiliations
Danielle Ashworth
Department of Women and Children’s Health, School of Life Course Sciences, King’s College London
Cheryl Battersby
Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London
Debra Bick
Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick
Marcus Green
Action On Pre-Eclampsia
Pollyanna Hardy
National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford
Lisa Leighton
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham
Laura A. Magee
Institute of Women and Children’s Health, King’s College London
Alisha Maher
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham
Richard J. McManus
Nuffield Department of Primary Care Health Sciences, University of Oxford
Catherine Moakes
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham
R. Katie Morris
Birmingham Clinical Trials Unit, Institute of Applied Health Research, University of Birmingham
Catherine Nelson-Piercy
Obstetric Medicine, Guy’s and St Thomas’ Hospitals NHS Trust
Jenie Sparkes
Department of Women and Children’s Health, School of Life Course Sciences, King’s College London
Oliver Rivero-Arias
National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford
Andrew Webb
Clinical Pharmacology, School of Cardiovascular and Metabolic Medicine & Sciences, King’s College London British Heart Foundation Centre of Research Excellence
Hannah Wilson
Department of Women and Children’s Health, School of Life Course Sciences, King’s College London
Jenny Myers
Faculty of Biology, Medicine and Health, The University of Manchester
Lucy C. Chappell
Department of Women and Children’s Health, School of Life Course Sciences, King’s College London
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.
