PREPARE, Prematurity Reduction by Pre-eclampsia Care (PREPARE)

July 16, 2023 updated by: Marcos Augusto Bastos Dias, Instituto Fernandes Figueira
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

1250

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Rio de Janeiro, Brazil, 20021140
        • Instituto Fernandes Figueira
      • Rio de Janeiro, Brazil, 20211-340
        • Maternidade Maria Amelia Buarque de Holanda
      • Rio de Janeiro, Brazil, 22775-003
        • Maternidade Leila Diniz
      • Sao Paulo, Brazil, 03015-000
        • Hospital Maternidade Leonor Mendes de Barros
    • Rio Gde Do Sul
      • Porto Alegre, Rio Gde Do Sul, Brazil, 90.035-903
        • Hospital de Clinicas de Porto Alegre
    • SAO Paulo
      • Botucatu, SAO Paulo, Brazil, 18618-681
        • Maternidade Unesp Botucatu
      • Campinas, SAO Paulo, Brazil, 13084-881
        • Caism - Unicamp
      • Santos, SAO Paulo, Brazil, 11045-904
        • Hospital Guilherme Alvaro

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

10 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • pregnancy before 16 weeks
  • delivery at designed maternity center

Exclusion Criteria:

  • not viable fetus

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: INTERVENTION
Clinical protocol using FullPIERS and sFlit/PLGF ratio (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio)
Diagnostic test: FullPIERS and sFlit/PLGF (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio)
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.
No Intervention: CONTROL
Usual clinic control

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
patients with preterm preeclampsia
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
proportion of women delivered in the centres with preterm pre-eclampsia (deliveries with preterm pre-eclampsia/ total deliveries), where preterm is <37 weeks' gestation
researchers will be assessing and reporting outcome through month 1 to month 34 of the study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of women delivered in the centers who delivered prematurely
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
proportion of women delivered with preterm pre-eclampsia/ total deliveries for pre-eclampsia, where preterm is <37 weeks' gestation
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
proportion of women delivered in the centres with preterm pre-eclampsia
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
proportion of women delivered in the centres with preterm pre-eclampsia (deliveries with preterm pre-eclampsia/ total deliveries), where preterm is <34 weeks' gestation
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
RATE PRETERM PRE-ECLAMPSIA DELIVERIES
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
proportion of women delivered with preterm pre-eclampsia/ total deliveries for pre-eclampsia, where preterm is <34 weeks' gestation
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
maternal morbidity and mortality defined as a composite of maternal mortality and features of 4a-4f
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study

4a. HELLP syndrome cases of HELLP syndrome in women with pre-eclampsia

4b. pulmonary oedema cases of pulmonary oedema in women with pre-eclampsia

4c. eclampsia proportion of women with eclampsia

4d. cerebrovascular accident (CVA) cases of maternal cerebrovascular accident (stroke or coma) in women with pre-eclampsia

4e. renal dysfunction cases of renal dysfunction in women with pre-eclampsia, where criteria is serum creatinine of >150
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
frequency of severe hypertension
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
systolic BP ≥ 160 mmHg or diastolic BP ≥ 110 mm/Hg
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
placental abruption
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
cases of placental abruption
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
mode of delivery (total C-sections)
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
total number of reported C-sections
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
stillbirth
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
cases of stillbirth at >20 weeks
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
early neonatal mortality
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
cases of neonatal mortality at <7 days
researchers will be assessing and reporting outcome through month 1 to month 34 of the study
admission to the neonatal care unit
Time Frame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
cases of admission to the neonatal care unit due to prematurity related to pre-eclampsia
researchers will be assessing and reporting outcome through month 1 to month 34 of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Fernandes Figueira

Collaborators

Hospital de Clinicas de Porto Alegre
University of Campinas, Brazil
UPECLIN HC FM Botucatu Unesp
CoLab
SMSDC/RJ
HGA
HOSPITAL MATERNIDADE LEONOR MENDES DE BARROS

Investigators

  • Principal Investigator: Marcos A Dias, PhD, Instituto Fernandes Figueira

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2016

Primary Completion (Actual)

December 30, 2019

Study Completion (Actual)

June 20, 2020

Study Registration Dates

First Submitted

February 21, 2017

First Submitted That Met QC Criteria

March 2, 2017

First Posted (Actual)

March 8, 2017

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

July 16, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRES-023-PPE-15

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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