PRECOG: Preeclampsia Ratio (sFlt-1/PlGF)

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT03289611

Collaborator

INSERM CESP1018 (Other)

Enrollment

Location

Arms

28.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the PRECOG study is to determine in a prospective interventional randomized study whether the implementation of a predictive test based on the sFLT-1/PlGF ratio improves perinatal care and reduces costs, in patients with suspected preeclampsia before 35 weeks of gestation.

Condition or Disease	Intervention/Treatment	Phase
Preeclampsia	Biological: sFlt-1 / PlGF ratio	N/A

Detailed Description

Preeclampsia is a hypertensive disorder of pregnancy associated with placental insufficiency and is one of the major important of prematurity and maternal mortality worldwide. It complicates 2 to 7% of pregnancies. It is currently considered that preeclampsia is associated with maternal endothelial dysfunction induced by the release into the maternal circulation of excess placental factors (such as sFLT-1 a soluble receptor for VEGF and PlGF). There is currently no curative treatment, and only childbirth and delivery of the placenta alleviate the mother's symptoms. Moreover, the evolution from case with mild symptoms to a severe case of preeclampsia is often is often rapid and difficult to anticipate. Therefore, it is recommended to manage patients with preeclampsia in hospital and cases of suspected preeclampsia are usually admitted in prenatal units. Each year thousands of patients are hospitalized for surveillance and blood/urine analysis to rule out the diagnosis of preeclampsia. A biological test to predict preeclampsia would therefore be of particular interest in order to:

identify patients without preeclampsia and therefore void costs and iatrogenic complications related to unnecessary hospitalization
identify patients at high risk of maternal and perinatal complications in order to anticipate in utero transfer, optimize maternal and fetal surveillance and administrate steroids.

It has recently been demonstrated that sFLT-1 and PlGF have a high predictive value for the diagnosis and the prediction of preeclampsia, but the interest of introducing these markers in clinical practice has not been demonstrated yet. The diagnostic and predictive value of the sFlt-1/PlGF ratio in patients at risk of placenta-related disorders has been shown in the recent literature and estimation of the sFlt-1/PlGF ratio has become an additional tool in the management of these disorders, primarily PE. This ratio can distinguish the patients that develop maternal or perinatal complications in the next 7-14 days from those with uncomplicated pregnancy. Women with an sFlt-1/PlGF ratio<38 do not have PE at the time of the test and in all likelihood will not develop PE for at least 1week; it is thereby of great value for reassuring the clinician and the patient. Up to 80% of patients are supposed to be in this patient group; therefore, clinicians are able to exclude the majority of patients and focus on those who need more attention and care. On contrary women with a sFlt-1/PlGF ratio > 38 and more specifically those with a ratio over 85 are highly likely to develop preeclampsia and should be managed according to local practice/guidelines. Thus the use of such predictive tool appear very promising but its interest has not been demonstrated in prospective intervention studies.

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

Preeclampsia Ratio (sFlt-1/PlGF) Evaluation for Clinical and Obstetrical Guidance

Actual Study Start Date :

Apr 26, 2018

Actual Primary Completion Date :

Aug 27, 2020

Actual Study Completion Date :

Aug 27, 2020

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Control Usual management
Experimental: Experimental Ambulatory management if sFlt-1 / PlGF ratio is below 38 Usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued	Biological: sFlt-1 / PlGF ratio Ambulatory management if sFlt-1 / PlGF ratio is below 38 usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued

Arm

Intervention/Treatment

No Intervention: Control

Usual management

Experimental: Experimental

Ambulatory management if sFlt-1 / PlGF ratio is below 38 Usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued

Biological: sFlt-1 / PlGF ratio

Ambulatory management if sFlt-1 / PlGF ratio is below 38 usual management if sFlt-1/PlGF is between 38 and 85. If the ratio is > 85, monitoring will be intensified and patient hospitalization will be continued

Outcome Measures

Primary Outcome Measures

number of patients hospitalised for more than 24 hours [up to 12 weeks]
Duration in hours, from admission to discharge from hospital at initial hospitalisation

Secondary Outcome Measures

Maternal and fetal morbidity [up to 13 weeks]
severe preeclampsia, eclampsia, HELLP syndrome, Disseminated intravascular coagulation, abruptio placenta, delivery before 34 WA, IUGR< 3°P, Fetal death
Maternal morbidity [up to 13 weeks]
High blood pressure, preeclampsia, caesarean section, postpartum hemorrhage> 500 ml
Severe Maternal morbidity (Composite outcome ) [up to 13 weeks]
eclampsia, HELLP syndrome, Disseminated intravascular coagulation, Abruption placenta
Number of days between randomisation and delivery [up to 12 weeks]
Number of days between randomisation and delivery
Mode of delivery [At delivery]
Cesarean, vaginal delivery
Gestational age [at delivery]
Gestational age at delivery
Birth weight centile [At delivery]
Centile of birth weight
Fetal death [up to 13 weeks]
Fetal death diagnosed at ultrasound before delivery
Prematurity before 37 WG [up to 13 weeks]
Delivery before 37 WG + 0 days
Prematurity before 34 WG [Delivery]
Delivery before 34 WG + 0 days
Prematurity before 32 WG [Delivery]
Delivery before 32 WG + 0 days
Perinatal morbidity (Composite outcome) [At delivery]
prematurity, birth weight <10 ° P
Severe Perinatal morbidity (Composite outcome) [At delivery]
perinatal mortality, prematurity <34 SA, birth weight <3 ° P
Costs [up to 14 weeks]
direct costs of prenatal care, direct costs of neonatal care, total costs
Satisfaction form [Day 3 after delivery]
Satisfaction concerning the management of pregnancy and duration of hospitalisation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient hospitalized for suspected preeclampsia between 24WG+ 0 days and 35WG + 6 days,

Patiente with at least one of the following criteria:

Arterial hypertension defined by systolic BP ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg
Proteinuria greater than 0.3g / 24h or 0.3g / l or ≥ 3+
Proteinuria / creatinine ratio ≥ 30 mg / mmol
Pain in the epigastric bar
Generalized edema
Hepatic cytolysis> 1.5N
Thrombocytopenia <150000 / mm3 Informed consent signed by both parties Non-opposition was accepted by parental authority Age ≥ 18 years

Exclusion Criteria:

Diagnosis of preeclampsia (arterial pressure> 140/90 and proteinuria> 0.3g / 24h or urine test> 3+) or complete HELLP syndrome (Platelets <100000 / mm3 and SGOT> 2N and LDH and collapsed Haptoglobin)

IUGR with absent or reverse diastolic umbilical flow

Fetal heart rate abnormalities

Gestational age <24 WG and> 35 WG

Multiple pregnancy

Patient without health insurance

Non-consent of patient

Minor patient

Congenital malformation