Giant PANDA Trial

In women with pregnancy hypertension (P), what is the effect of a treatment strategy with nifedipine (I) versus labetalol (C) on severe maternal hypertension (O) and a composite of fetal or neonatal death, or neonatal unit admissions (O)?

A prospective, late phase, pragmatic, parallel group, open-label, multicentre, two-arm randomised controlled trial. Women who decline randomisation or are unable to be randomised (due to contraindications to either labetalol or nifedipine or women taking both drugs and not able to be randomised to a single drug) will be offered participation in an observational study, involving data collection only.

To evaluate the effect of different antihypertensive drugs in women with pregnancy hypertension on maternal and fetal/neonatal outcomes.

Primary Objective: 

To Evaluate if treatment with nifedipine (clacium channel blocker), compared to labetalol (mixed alpha/beta blocker) in women with pregnancy hypertension, reduces severe maternal hypertension without increasing fetal or neonatal death, or neonatal unit admission.

Secondary Objectives: 

To investigate the effect of treatment with nifedipine versus labetalol on other secondary maternal and fetal/neonatal outcomes including patient-reported outcome measures. 

To evaluate the cost-effectiveness of nifedipine versus labetalol as antihypertensive drugs from an NHS perspective.

The study will be conducted in around 50 consultant-led maternity units across the UK.

2,300 pregnant women with hypertension.

Treatment with any preparation of modified release nifedipine, a calcium channel blocker, (intervention arm) versus any preparation of labetalol, a mixed alpha/beta blocker, (active control arm) by random allocation (1:1). 

All other aspects of antenatal and delivery care will follow usual clinical care pathways underpinned by NICE 2019 guidelines for pregnancy hypertension.

Primary maternal outcome: Severe hypertension (proportion of days with a healthcare professional measured systolic blood pressure reading ≥160 mmHg between randomisation and birth). Primary fetal/neonatal outcome: 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 maternal and fetal/neonatal outcomes include clinical and patient-reported outcomes in addition to health care resource use.

This study is funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and sponsored by the University of Birmingham. The Chief Investigator, Professor Lucy Chappell, is based at King’s College London and she is running the study with the Birmingham Clinical Trials Unit.