Clinical trial NCT03289611: Preeclampsia Ratio (sFlt-1/PlGF)
Official title: Preeclampsia Ratio (sFlt-1/PlGF) Evaluation for Clinical and Obstetrical Guidance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preeclampsia
Keywords: Preeclampsia
pregnancy
biomarkers
prediction
safety
cost
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2017-09-21
Enrollment: 84
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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.

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.

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 WG. costs, in patients with suspected preeclampsia before 35 WG.

Eligibility criteria: 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

Primary outcomes:
measure: number of patients hospitalised for more than 24 hours
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Maternal and fetal morbidity
timeFrame: up to 13 weeks
measure: Maternal morbidity
timeFrame: up to 13 weeks
measure: Severe Maternal morbidity (Composite outcome )
timeFrame: up to 13 weeks
measure: Number of days between randomisation and delivery
timeFrame: up to 12 weeks
measure: Mode of delivery
timeFrame: At delivery
measure: Gestational age
timeFrame: at delivery
measure: Birth weight centile
timeFrame: At delivery
measure: Fetal death
timeFrame: up to 13 weeks
measure: Prematurity before 37 WG
timeFrame: up to 13 weeks
measure: Prematurity before 34 WG
timeFrame: Delivery
measure: Prematurity before 32 WG
timeFrame: Delivery
measure: Perinatal morbidity (Composite outcome)
timeFrame: At delivery
measure: Severe Perinatal morbidity (Composite outcome)
timeFrame: At delivery
measure: Costs
timeFrame: up to 14 weeks
measure: Satisfaction form
timeFrame: Day 3 after delivery
Other outcomes:
Locations:
city: Paris
country: France
facility: CHU Cochin, Maternité Port Royal
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Jean GUIBOURDENCHE, MD, PhD
role: STUDY_CHAIR
References:
citation: Tsatsaris V, Goffin F, Munaut C, Brichant JF, Pignon MR, Noel A, Schaaps JP, Cabrol D, Frankenne F, Foidart JM. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab. 2003 Nov;88(11):5555-63. doi: 10.1210/jc.2003-030528.
citation: Sibiude J, Guibourdenche J, Dionne MD, Le Ray C, Anselem O, Serreau R, Goffinet F, Tsatsaris V. Placental growth factor for the prediction of adverse outcomes in patients with suspected preeclampsia or intrauterine growth restriction. PLoS One. 2012;7(11):e50208. doi: 10.1371/journal.pone.0050208. Epub 2012 Nov 28.
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.