PREPARE, Prematurity Reduction by Pre-eclampsia Care
Condition: Pre-Eclampsia; Premature Birth
MeSH terms: Premature Birth; Eclampsia; Pre-Eclampsia
Study type: Interventional

Summary: 
      Investigators will test a novel system of integrated care, to promote the use of the WORLD
      HEALTH ORGANIZATION Guidelines for the management of pre-eclampsia and initiate the use of a
      structured risk assessment strategy to reduce the incidence of preterm delivery from
      pre-eclampsia by providing obstetricians with the confidence to safely defer delivery of
      women with pre-eclampsia, identified to be of low risk.
    

Detailed description: 
      This proposal (PREPARE), led by Brazilian investigators in collaboration with the Global
      Pregnancy Collaboration (CoLab) is centred on 7 hospital centres and their 23 satellite
      community health centres (UBSs). There are two clinical initiatives: First, a programme of
      systematic knowledge transfer (KT) to encourage adoption of the WHO Guidelines to prevent
      pre-eclampsia as part of routine antenatal care (Objective 1); second an intervention to
      reduce unnecessary preterm deliveries for the management of pre-eclampsia. CoLab
      investigators have developed methods to identify those women with preterm pre-eclampsia whose
      pregnancies can be safely prolonged.4-6 In Objective 2.1, these methods will be applied to
      women presenting with definite or suspected pre-eclampsia at < 37 weeks' gestation.
      Investigators will determine the likelihood of an imminent adverse outcome in these women
      using Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio (sFlT-1/PlGF)
      measurement and fullPIERS clinical assessment. Prior studies with these approaches indicate
      more than 98% negative predictive value for adverse outcomes for both.4-6 Investigators will
      delay delivery in those whose risk is low, caring for patients in accordance with
      evidence-based WHO guidelines.Unlike medications, management cannot be tested in a blinded
      way. Management needs integrated skills and commitment from caregivers. Hence, a standard
      randomized controlled trial is inappropriate. Instead investigators propose a Stepped Wedge
      Design to study outcomes in the 7 geographically diverse study centres, throughout Brazil. At
      least 6 women with preterm pre-eclampsia will deliver at each centre every month. The primary
      outcome will be a lower rate of PRETERM BIRTH due to pre-eclampsia as a proportion of total
      deliveries in the centre(s) after implementation of the plan compared to prior to its
      introduction. The study will have 80% power to demonstrate a 25% reduction (2.0 - 1.5%).
      Investigators will assess maternal and foetal adverse events as secondary outcomes. Objective
      2.2 will institute an intense program of knowledge transfer to implement the new management
      techniques. In Objectives 2.3 and 2.4 will determine patient and provider satisfaction and
      the economic impact of the care plan. In Objective 3 will establish a biobank and database to
      begin to assess demographic factors and biological analytes that may help identify unique
      predictive and diagnostic/pathophysiological features for pre-eclampsia in the Brazilian
      population (that may extend to other low and middle income countries (LMIC)). For two years
      at routine visits (≤16 weeks, 28-32 weeks) at each UBS, relevant data and plasma, serum,
      urine and DNA samples will be stored to the appropriate standards in the biorepository (at
      least 7000 cases). Investigators estimate that will acquire samples at delivery in at least
      5000 of these women. For four years, biological samples from women with pre-eclampsia or
      other adverse outcomes and 2 matched controls will be collected at admission for labour (an
      additional 3,000 subjects). Objective 4 will initiate pilot studies to identify novel
      biomarkers, and compare these and other known pathophysiological factors with those from LMIC
      (Africa, India) and HIC using samples from CoLab. Additional funding will be sought for
      expansion and validation (e.g. Merck for Mothers). Investigators will also seek funding to
      address risk stratification in apparently low risk women, based on the samples collected at
      28-32 weeks. Objective 5 will promote intellectual interactions and collaboration between the
      seven centres and CoLab. Ability to understand and cure complex adverse pregnancy outcomes
      leading to acute and long-range disability in children requires intensive collaboration
      across usual "silos" including hospitals and nations. The coordinators anticipate the
      interaction of investigators and care providers in the seven centres will foster intellectual
      collaboration and improved standardized care. Brazilian investigators will become members of
      CoLab, increasing its unique vision, expertise and resources (current data and biological
      materials from 28 centres). worldwide).
    

Intervention name(s): FullPIERS and sFlit/PLGF (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio)
Intervention type(s): Diagnostic Test
Intervention description(s): Once the centre is randomised to receive the intervention, all eligible women will have serum sFlt1/PlGF measurement performed and fullPIERS assessment and both results will be revealed to the care providers. This will include all women with pre-eclampsia or suspected pre-eclampsia cared for at the main hospital centres (and not be limited to women referred to the hospital from the community health centres). sFlt-1/PlGF will be tested by immunoassays (Roche Platform®). The result read out is provided by specific machines provided by Roche in less than one hour, which permits rapid clinical decision-making. Risk stratification using fullPIERS will be performed on tablet computers using a pre-defined risk scoring system integrated within the MedSciNet database.
Intervention MeSH terms: Mitogens
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: stepped-wedge cluster-randomised trial in seven clusters
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Preterm Infants; Premature Birth; Placenta growth factor; Prenatal Care; PERINATAL MORTALITY; Pre-Eclampsia