PREPARE, Prematurity Reduction by Pre-eclampsia Care

NCT ID: NCT03073317

Last Updated: 2023-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2020-06-20

Brief 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).

Conditions

Pre-Eclampsia; Premature Birth

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

INTERVENTION

Clinical protocol using FullPIERS and sFlit/PLGF ratio (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio)

Group Type: EXPERIMENTAL

FullPIERS and sFlit/PLGF (Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio)

Intervention Type: DIAGNOSTIC_TEST

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.

CONTROL

Usual clinic control

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• pregnancy before 16 weeks
• delivery at designed maternity center

Exclusion Criteria

• not viable fetus

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

CoLab

UNKNOWN

Sponsor Role: collaborator

SMSDC/RJ

UNKNOWN

Sponsor Role: collaborator

University of Campinas, Brazil

OTHER

Sponsor Role: collaborator

UPECLIN HC FM Botucatu Unesp

OTHER

Sponsor Role: collaborator

HGA

UNKNOWN

Sponsor Role: collaborator

HOSPITAL MATERNIDADE LEONOR MENDES DE BARROS

UNKNOWN

Sponsor Role: collaborator

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: collaborator

Instituto Fernandes Figueira

OTHER_GOV

Sponsor Role: lead

Responsible Party

Marcos Augusto Bastos Dias

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marcos A Dias, PhD

Role: PRINCIPAL_INVESTIGATOR

Instituto Fernandes Figueira

Locations

Hospital de Clinicas de Porto Alegre

Porto Alegre, RIO GDE DO SUL, Brazil

Maternidade Unesp Botucatu

Botucatu, São Paulo, Brazil

Caism - Unicamp

Campinas, São Paulo, Brazil

Hospital Guilherme Alvaro

Santos, São Paulo, Brazil

Instituto Fernandes Figueira

Rio de Janeiro, , Brazil

Maternidade Maria Amelia Buarque de Holanda

Rio de Janeiro, , Brazil

Maternidade Leila Diniz

Rio de Janeiro, , Brazil

Hospital Maternidade Leonor Mendes de Barros

São Paulo, , Brazil

Countries

Brazil

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Other Identifiers

PRES-023-PPE-15

Identifier Type: -

Identifier Source: org_study_id