Preeclampsia Ratio (sFlt-1/PlGF)

Preeclampsia Clinical Trial

— PRECOG  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03289611
• Other study ID #: P161101
• Status: Completed
• Phase: N/A
• Start date: April 26, 2018
• Est. completion date: August 27, 2020

Study information

• Verified date: July 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: August 27, 2020
• Est. primary completion date: August 27, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pre-Eclampsia
• Preeclampsia

Intervention

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

Locations

Country	Name	City	State
France	CHU Cochin, Maternité Port Royal	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	INSERM CESP1018

Country where clinical trial is conducted

France, 

References & Publications (3)

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. — View 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. — View Citation

Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennström 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of patients hospitalised for more than 24 hours	Duration in hours, from admission to discharge from hospital at initial hospitalisation	up to 12 weeks
Secondary	Maternal and fetal morbidity	severe preeclampsia, eclampsia, HELLP syndrome, Disseminated intravascular coagulation, abruptio placenta, delivery before 34 WA, IUGR< 3°P, Fetal death	up to 13 weeks
Secondary	Maternal morbidity	High blood pressure, preeclampsia, caesarean section, postpartum hemorrhage> 500 ml	up to 13 weeks
Secondary	Severe Maternal morbidity (Composite outcome )	eclampsia, HELLP syndrome, Disseminated intravascular coagulation, Abruption placenta	up to 13 weeks
Secondary	Number of days between randomisation and delivery	Number of days between randomisation and delivery	up to 12 weeks
Secondary	Mode of delivery	Cesarean, vaginal delivery	At delivery
Secondary	Gestational age	Gestational age at delivery	at delivery
Secondary	Birth weight centile	Centile of birth weight	At delivery
Secondary	Fetal death	Fetal death diagnosed at ultrasound before delivery	up to 13 weeks
Secondary	Prematurity before 37 WG	Delivery before 37 WG + 0 days	up to 13 weeks
Secondary	Prematurity before 34 WG	Delivery before 34 WG + 0 days	Delivery
Secondary	Prematurity before 32 WG	Delivery before 32 WG + 0 days	Delivery
Secondary	Perinatal morbidity (Composite outcome)	prematurity, birth weight <10 ° P	At delivery
Secondary	Severe Perinatal morbidity (Composite outcome)	perinatal mortality, prematurity <34 SA, birth weight <3 ° P	At delivery
Secondary	Costs	direct costs of prenatal care, direct costs of neonatal care, total costs	up to 14 weeks
Secondary	Satisfaction form	Satisfaction concerning the management of pregnancy and duration of hospitalisation	Day 3 after delivery