Clinical trial NCT03073317: PREPARE, Prematurity Reduction by Pre-eclampsia Care
Official title: PREPARE, Prematurity Reduction by Pre-eclampsia Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pre-Eclampsia
Premature Birth
Keywords: Preterm Infants
Premature Birth
Placenta growth factor
Prenatal Care
PERINATAL MORTALITY
Pre-Eclampsia
Lead sponsor: Instituto Fernandes Figueira
Sponsor class: OTHER_GOV
Collaborators: name: CoLab
name: SMSDC/RJ
name: University of Campinas, Brazil
name: UPECLIN HC FM Botucatu Unesp
name: HGA
name: HOSPITAL MATERNIDADE LEONOR MENDES DE BARROS
name: Hospital de Clinicas de Porto Alegre
First posted: 2017-03-08
Enrollment: 1250
Sex: FEMALE
Minimum age (years): 10
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: stepped-wedge cluster-randomised trial in seven clusters
Primary purpose: PREVENTION

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).

Eligibility criteria: Inclusion Criteria:

* pregnancy before 16 weeks
* delivery at designed maternity center

Exclusion Criteria:

* not viable fetus

Primary outcomes:
measure: patients with preterm preeclampsia
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
Secondary outcomes:
measure: proportion of women delivered in the centers who delivered prematurely
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: proportion of women delivered in the centres with preterm pre-eclampsia
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: RATE PRETERM PRE-ECLAMPSIA DELIVERIES
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: maternal morbidity and mortality defined as a composite of maternal mortality and features of 4a-4f
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: frequency of severe hypertension
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: placental abruption
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: mode of delivery (total C-sections)
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: stillbirth
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: early neonatal mortality
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
measure: admission to the neonatal care unit
timeFrame: researchers will be assessing and reporting outcome through month 1 to month 34 of the study
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Gde Do Sul
city: Botucatu
country: Brazil
facility: Maternidade Unesp Botucatu
state: SAO Paulo
city: Campinas
country: Brazil
facility: Caism - Unicamp
state: SAO Paulo
city: Santos
country: Brazil
facility: Hospital Guilherme Alvaro
state: SAO Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Fernandes Figueira
city: Rio de Janeiro
country: Brazil
facility: Maternidade Maria Amelia Buarque de Holanda
city: Rio de Janeiro
country: Brazil
facility: Maternidade Leila Diniz
city: Sao Paulo
country: Brazil
facility: Hospital Maternidade Leonor Mendes de Barros
Study officials:
affiliation: Instituto Fernandes Figueira
name: Marcos A Dias, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med. 2016 Jan 7;374(1):13-22. doi: 10.1056/NEJMoa1414838.
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