Dataset Information

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.

SUBMITTER: Chappell LC

PROVIDER: S-EPMC6350286 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chappell Lucy C LC Green Marcus M Marlow Neil N Sandall Jane J Hunter Rachael R Robson Stephen S Bowler Ursula U Chiocchia Virginia V Hardy Pollyanna P Juszczak Edmund E Linsell Louise L Placzek Anna A Brocklehurst Peter P Shennan Andrew A

Trials 20190128 1

<h4>Background</h4>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 ...[more]

PMID: 30691508

Similar Datasets

Project description:BackgroundIn women with late preterm pre-eclampsia, the optimal time to initiate delivery is unclear because limitation of maternal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of neonatal or infant outcomes, compared with expectant management (usual care) in women with late preterm pre-eclampsia.MethodsIn this parallel-group, non-masked, multicentre, randomised controlled trial done in 46 maternity units across England and Wales, we compared planned delivery versus expectant management (usual care) with individual randomisation in women with late preterm pre-eclampsia from 34 to less than 37 weeks' gestation and a singleton or dichorionic diamniotic twin pregnancy. The co-primary maternal outcome was a composite of maternal morbidity or recorded systolic blood pressure of at least 160 mm Hg with a superiority hypothesis. The co-primary perinatal outcome was a composite of perinatal deaths or neonatal unit admission up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were by intention to treat, together with a per-protocol analysis for the perinatal outcome. The trial was prospectively registered with the ISRCTN registry, ISRCTN01879376. The trial is closed to recruitment but follow-up is ongoing.FindingsBetween Sept 29, 2014, and Dec 10, 2018, 901 women were recruited. 450 women (448 women and 471 infants analysed) were allocated to planned delivery and 451 women (451 women and 475 infants analysed) to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group (289 [65%] women) compared with the expectant management group (338 [75%] women; adjusted relative risk 0·86, 95% CI 0·79-0·94; p=0·0005). The incidence of the co-primary perinatal outcome by intention to treat was significantly higher in the planned delivery group (196 [42%] infants) compared with the expectant management group (159 [34%] infants; 1·26, 1·08-1·47; p=0·0034). The results from the per-protocol analysis were similar. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group.InterpretationThere is strong evidence to suggest that planned delivery reduces maternal morbidity and severe hypertension compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater neonatal morbidity. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision making on timing of delivery.FundingNational Institute for Health Research Health Technology Assessment Programme.

Project description:BackgroundPre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity globally. Planned delivery between 34+0 and 36+6 weeks may reduce adverse pregnancy outcomes but is yet to be evaluated in a low and middle-income setting. Prior to designing a randomised controlled trial to evaluate this in India and Zambia, we carried out a 6-month feasibility study in order to better understand the proposed trial environment and guide development of our intervention.MethodsWe used mixed methods to understand the disease burden and current management of pre-eclampsia at our proposed trial sites and explore the acceptability of the intervention. We undertook a case notes review of women with pre-eclampsia who delivered at the proposed trial sites over a 3-month period, alongside facilitating focus group discussions with women and partners and conducting semi-structured interviews with healthcare providers. Descriptive statistics were used to analyse audit data. A thematic framework analysis was used for qualitative data.ResultsCase notes data (n = 326) showed that in our settings, 19.5% (n = 44) of women with pre-eclampsia delivering beyond 34 weeks experienced an adverse outcome. In women delivering between 34+0 and 36+6 weeks, there were similar numbers of antenatal stillbirths [n = 3 (3.3%)] and neonatal deaths [n = 3 (3.4%)]; median infant birthweight was 2.2 kg and 1.9 kg in Zambia and India respectively. Lived experience of women and healthcare providers was an important facilitator to the proposed intervention, highlighting the serious consequences of pre-eclampsia. A preference for spontaneous labour and limited neonatal resources were identified as potential barriers.ConclusionsThis study demonstrated a clear need to evaluate the intervention and highlighted several challenges relating to trial context that enabled us to adapt our protocol and design an acceptable intervention. Our study demonstrates the importance of assessing feasibility when developing complex interventions, particularly in a low-resource setting. Additionally, it provides a unique insight into the management of pre-eclampsia at our trial settings and an understanding of the knowledge, attitudes and beliefs underpinning the acceptability of planned early delivery.

Project description:BackgroundPre-eclampsia is a pregnancy complication characterised by high blood pressure and multi-organ dysfunction in the mother. It is a leading contributor to maternal and perinatal mortality, with 99% of these deaths occurring in low- and middle-income countries (LMIC). Whilst clear guidelines exist for management of early-onset (< 34 weeks) and term (≥ 37 weeks) disease, the optimal timing of delivery in pre-eclampsia between 34+ 0 and 36+ 6 weeks is less clear. In a high-income setting, delivery may improve maternal outcomes without detriment to the baby, but this intervention is yet to be evaluated in LMIC.MethodsThe CRADLE-4 Trial is a non-masked, randomised controlled trial comparing planned early delivery (initiation of delivery within 48 h of randomisation) with routine care (expectant management) in women with pre-eclampsia between 34+ 0 and 36+ 6 weeks' gestation in India and Zambia. The primary objective is to establish whether a policy of planned early delivery can reduce adverse maternal outcomes, without increasing severe neonatal morbidity.DiscussionThe World Health Organization recommends delivery for all women with pre-eclampsia from 37 weeks onwards, based on evidence showing clear maternal benefit without increased neonatal risk. Before 34 weeks, watchful waiting is preferred, with delivery recommended only when there is severe maternal or fetal compromise, due to the neonatal risks associated with early preterm delivery. Currently, there is a lack of guidance for clinicians managing women with pre-eclampsia between 34+ 0 and 36+ 6 weeks. Early delivery benefits the mother but may increase the need for neonatal unit admission in the infant (albeit without serious morbidity at this gestation). On the other hand, waiting to deliver may increase the risk of stillbirth, fetal growth restriction and hypoxic brain injury in the neonate as a result of severe maternal complications. This is especially true for LMIC where there is a higher prevalence of adverse events. The balance of risks and benefits therefore needs to be carefully assessed before making firm recommendations. This is the first trial evaluating the optimal timing of delivery in pre-eclampsia in LMIC, where resources and disease burden are considerably different.Trial registrationISRCTN 10672137 . Registered on 28 November 2019.

Project description:ObjectiveTo evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia.DesignRandomised, double blind, placebo controlled trial.SettingReferral hospital in Cape Town, South Africa.Participants180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks' gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo.Intervention3 g of oral extended release metformin or placebo daily, in divided doses, until delivery.Main outcome measureThe primary outcome was prolongation of gestation.ResultsOf 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm.ConclusionsThis trial suggests that extended release metformin can prolong gestation in women with preterm pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible.Trial registrationPan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/.

Project description:OBJECTIVES:Pregnancy hypertension is the third leading cause of maternal mortality in Mozambique and contributes significantly to fetal and neonatal mortality. The objective of this trial was to assess whether task-sharing care might reduce adverse pregnancy outcomes related to delays in triage, transport, and treatment. STUDY DESIGN:The Mozambique Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trial (NCT01911494) recruited pregnant women in 12 administrative posts (clusters) in Maputo and Gaza Provinces. The CLIP intervention (6 clusters) consisted of community engagement, community health worker-provided mobile health-guided clinical assessment, initial treatment, and referral to facility either urgently (<4hrs) or non-urgently (<24hrs), dependent on algorithm-defined risk. Treatment effect was estimated by multi-level logistic regression modelling, adjusted for prognostically-significant baseline variables. Predefined secondary analyses included safety and evaluation of the intensity of CLIP contacts. MAIN OUTCOME MEASURES:20% reduction in composite of maternal, fetal, and newborn mortality and major morbidity. RESULTS:15,013 women (15,123 pregnancies) were recruited in intervention (N = 7930; 2·0% loss to follow-up (LTFU)) and control (N = 7190; 2·8% LTFU) clusters. The primary outcome did not differ between intervention and control clusters (adjusted odds ratio (aOR) 1·31, 95% confidence interval (CI) [0·70, 2·48]; p = 0·40). Compared with intervention arm women without CLIP contacts, those with ?8 contacts experienced fewer primary outcomes (aOR 0·79 (95% CI 0·63, 0·99); p = 0·041), primarily due to improved maternal outcomes (aOR 0·72 (95% CI 0·53, 0·97); p = 0·033). INTERPRETATION:As generally implemented, the CLIP intervention did not improve pregnancy outcomes; community implementation of the WHO eight contact model may be beneficial. FUNDING:The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337).

Dataset Information

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

Background

Methods/design

Discussion

Trial registration

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets