Planned delivery or expectant management for late preterm pre-eclampsia: study protocol for a randomised controlled trial (PHOENIX trial)

Abstract

Background: Pre-eclampsia is a pregnancy disorder, characterised by hypertension and multisystem complications in the mother. The adverse outcomes of pre-eclampsia include severe hypertension, stroke, renal and hepatic injury, haemorrhage, fetal growth restriction and even death. The optimal time to instigate delivery to prevent morbidity when pre-eclampsia occurs between 34 and 37 weeks' gestation, without increasing problems related to infant immaturity or complications, remains unclear.

Methods/design: The PHOENIX trial is a non-masked, randomised controlled trial, comparing planned early delivery (with initiation of delivery within 48 h of randomisation) with usual care (expectant management) in women with pre-eclampsia between 34^{+ 0} and 36^{+ 6} weeks' gestation. The primary objectives of the trial are to determine if planned delivery reduces adverse maternal outcomes, without increasing the short-term harm to infants (composite of perinatal deaths or neonatal unit admissions up to infant hospital discharge) or impacting long-term infant neurodevelopmental status at 2 years corrected age (Parent Report of Cognitive Abilities-Revised).

Discussion: Current practice in the UK at the time of trial commencement for management of pre-eclampsia varies by gestation. Previous trials have shown that in women with pre-eclampsia after 37 weeks of gestion, delivery is initiated, as maternal complications are reduced without increasing fetal risks. Prior to 34 weeks of gestation, usual management aims to prolong pregnancy for fetal benefit, unless severe complications occur, necessitating preterm delivery. This trial aims to address the uncertainty for women where the balance of benefits and risks of delivery compared to expectant management are uncertain. Previous trials in this area have been undertaken, but have not provided a definitive answer, and the research question remains active. The results of this trial are expected to influence clinical practice internationally, through direct adoption and by incorporation into guidelines in countries with similar settings.

Trial registration: ISRCTN01879376 . Registered on 25 November 2013.

Keywords: Pre-eclampsia; hypertension; perinatal; pregnancy.

Fig. 1

Schedule of participant enrolment, interventions and assessments in the trial. PARCA-R Parent Report of Cognitive Abilities, Revised, SAE serious adverse event. 1 Screening to be conducted of all women suspected of being eligible for the study. 2 Delivery to be commenced within 48 hours of randomisation for women randomised to the planned delivery group. 3 Eligibility for study to be assessed from blood pressure recorded at the time the diagnosis of pre-eclampsia. 4 Blood systolic pressure reading within the 48 hours prior to randomisation to be recorded. 5 Highest systolic blood pressure recorded between randomisation and delivery to be recorded. 6 Highest systolic blood pressure recorded between delivery and discharge to be recorded. 7 Haematology and/or Biochemistry results that contributed to diagnosis of pre-eclampsia to be recorded. 8 The most recent Haematology and/or Biochemistry results prior to randomisation to be recorded. 9 Abnormal Haematology/ Biochemistry results from randomisation to discharge to be recorded at discharge. 10 Serious Adverse Events (SAEs) to be recorded from randomisation to post-natal discharge. Only unexpected SAEs to be reported. 11 Brief details of anti-hypertensive and medication for induction will be recorded; all other concomitant medication will only be recorded in the event that an unexpected Serious Adverse Event is reported. 12 EQ-5D-5L[10] to be given to the participant to complete immediately after randomisation