Impact of First-trimester Preeclampsia Screening on Perinatal and Maternal Morbidity (RANSPRE)

NCT ID: NCT05521776

Last Updated: 2025-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

14500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-06

Study Completion Date

2026-03-06

Brief Summary

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The purpose of this study is to determine whether first-trimester screening for preeclampsia based on the FMF algorithm (a combination of maternal clinical, sonographic and biochemical parameters), improves maternal or perinatal health.

Detailed Description

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Preeclampsia (PE) complicates 2% of pregnancies and is a leading cause of severe maternal and perinatal complications. There is no curative treatment, and the only recognized beneficial primary prevention is low-dose aspirin. Meta-analyses of randomized trials show that the administration of aspirin, started before 16 weeks of gestation (WG) and at the dosage of 100-160 mg/d in pregnant women at high risk of PE, is associated with a 50% to 60% reduction in the rates of PE, prematurity and perinatal mortality. The group of patients benefiting most from aspirin is pregnant women with a history of PE. That is why all guidelines recommend early preventive administration of aspirin in pregnant women with PE in a previous pregnancy. However, patients with a history of PE represent a small fraction of pregnant women, and PE mostly occurs in women who do not have a history of PE, especially nulliparas. Recently, several national societies decided to broaden the indications for aspirin prevention on the basis of the number of known maternal risk factors. These recommendations lead to a wide use of low-dose aspirin in up to 30% of pregnant women. In order to better target patients at risk of PE among all pregnant women, screening tests have been developed integrating clinical characteristics, uterine Doppler (UD) parameters and biomarkers in a single score. The study by Poon et al. paved the way for early detection of PE. An algorithm based on maternal characteristics, UD parameters and serum levels of PlGF and PAPP-A between 11 and 14 WG yielded detection rates of 93% and 36% for the prediction of early- and late-onset PE, respectively, at 5% false-positive rate (FPR), which were superior to the detection rates of the traditional checklist-based approach, which relies on maternal factors only. This algorithm developed by the Fetal Medicine Foundation (FMF) has since evolved and is now integrated in the combined test for PE screening known as the FMF triple test (a combination of maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and serum PlGF). In a subsequent study using a risk cutoff of 1 in 100 for the predicted probability of preterm PE, a screen-positive rate of 10% has been reported, with detection rates for early-onset, preterm, and term PE of 88%, 69%, and 40%, respectively.

Recently, the ASPRE study evaluated the impact of aspirin in patients identified at high risk of PE on the basis of this FMF test. Screening was offered to 26,941 women and identified 2,641 high-risk patients of whom 1,776 were randomized to aspirin or placebo. This trial showed a reduction in the incidence of PE \<37 WG, occurring in 13/798 in the aspirin group versus 35/822 in the placebo group (p=0.004), but with no significant effect on the overall rate of PE and most importantly on perinatal morbidity. Screening had to be applied to almost 27,000 women for a benefit of 22 avoided cases of preterm PE, with no demonstrated effect on the health of the women and children. The ASPRE study is important but does not demonstrate the benefit of routinely implementing PE screening in the general population. Indeed, there is currently no randomized study comparing a group of women to which the screening procedure would be applied to a group of women without screening, the only design able to provide strong evidence of a benefit. In addition, implementing a national screening program in pregnant women may induce adverse events, especially iatrogenicity (more hospitalizations, more ultrasound examinations, more consultations) and anxiety. Such a screening program is also associated with an increase of direct and indirect health costs.

To consider implementing screening for PE in the general population, it is then essential to demonstrate its benefits on robust health outcomes and not only on the PE diagnosis, as well as to assess its potential adverse consequences and costs. This evaluation is all the more crucial since it is currently offered to an increasing number of women.

The RANSPRE study will therefore be the first trial to test the impact on perinatal and maternal health outcomes of first-trimester screening for preeclampsia associated with aspirin treatment of pregnant women screened at risk. A medical and economic evaluation allowing a cost-effectiveness analysis will also be carried out. The results of this study will constitute essential information relevant to the health care system that will guide policymaking for the prevention of PE in the general population of pregnant women.

The primary objective of the study is to evaluate the impact of first-trimester PE screening (FTPS) on the incidence of severe perinatal morbidity. The primary outcome will be severe perinatal morbidity defined by a composite criterion including at least one of the following: perinatal mortality (stillbirth at or after 20 WG or neonatal death within 7 days of life) or prematurity \<34 WG or birth weight \<3° percentile for gestational age.

Secondary objectives are: (i) to evaluate the impact of first-trimester PE screening on: the incidence of preeclampsia, the incidence of components of moderate and severe maternal morbidity, the incidence of components of moderate and severe perinatal morbidity; (ii) to evaluate the impact of first-trimester PE screening on potential adverse events: iatrogenicity, over-medicalization, women's satisfaction and anxiety status; (iii) to evaluate the economic impact of first-trimester PE screening on costs.

Patients will be recruited in 22 maternity centers at university hospitals in France. The inclusion period during pregnancy is between 11 WG and 14 WG. Eligible women will be identified in early pregnancy at their first prenatal visit in the maternity hospital, before or at the time of the first-trimester ultrasound. The FMF algorithm used in the study for PE screening is based on a combination of maternal clinical parameters (medical history, maternal characteristics, pregnancy characteristics, mean arterial pressure), sonographic parameters (uterine Doppler with measurement of mean pulsatility index) and biochemical parameters (PlGF concentration). Women agreeing to participate in the RANSPRE trial will be randomized either to the experimental group with first-trimester screening for PE or to the control group with usual care without screening for PE.

All patients will be asked to complete self-administered questionnaires at 20 (+/2) WG and during the postpartum period (within 30 days after delivery) assessing women's satisfaction and women's anxiety. These questionnaires will be collected for women included until 31/01/2025.. A notebook will be given to patients screened at risk and with aspirin prescription to monitor aspirin observance and to record potential side-effects related to aspirin.

An intention-to-treat analysis will be performed as the principal analysis.

Conditions

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Preeclampsia (PE)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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With first trimester preeclampsia screening

Risk assessment of developing preeclampsia between 11 and 14 WG based on maternal parameters, blood pressure measurement, Doppler measurements of the uterine arteries and maternal PlGF concentration. Patients at high risk of preeclampsia are treated with aspirin.

Group Type EXPERIMENTAL

First-trimester preeclampsia screening (FMF triple test)

Intervention Type PROCEDURE

An algorithm assessing the risk of developing preeclampsia combining maternal parameters, blood pressure measurement, Doppler measurements of the uterine arteries and maternal PlGF concentrations.

For women in the screening group, a Doppler study of the uterine arteries and a blood test to quantify PlGF concentrations will be performed within 2 days of randomization, allowing the risk to be calculated according to the screening test. For women with a positive screening test (i.e. predicted risk\> 1/100), a treatment with aspirin will be prescribed at 160 mg/day, started as soon as possible and before 15 WG, and taken up to 36 WG, in the absence of contraindications. For women with negative screening, usual pregnancy monitoring without aspirin will be offered.

Without first trimester preeclampsia screening

Usual prenatal care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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First-trimester preeclampsia screening (FMF triple test)

An algorithm assessing the risk of developing preeclampsia combining maternal parameters, blood pressure measurement, Doppler measurements of the uterine arteries and maternal PlGF concentrations.

For women in the screening group, a Doppler study of the uterine arteries and a blood test to quantify PlGF concentrations will be performed within 2 days of randomization, allowing the risk to be calculated according to the screening test. For women with a positive screening test (i.e. predicted risk\> 1/100), a treatment with aspirin will be prescribed at 160 mg/day, started as soon as possible and before 15 WG, and taken up to 36 WG, in the absence of contraindications. For women with negative screening, usual pregnancy monitoring without aspirin will be offered.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Pregnancy between 11 and 14 WG
* Age ≥18 years
* Affiliated to or beneficiary of a health insurance system (including AME)
* Signed informed consent

Exclusion Criteria

* Gestational age \<11 WG and \>14 WG
* Known ectopic pregnancy
* Known non-ongoing pregnancy
* Known multiple pregnancy
* History of PE in a previous pregnancy
* Pregnancies complicated by major fetal abnormality identified at the first-trimester ultrasound if performed before randomization
* Absence of health insurance
* Contra-indication to aspirin (bleeding disorders such as von Willebrand's disease, active peptic ulceration, hypersensitivity to aspirin, active peptic ulceration, NSAID-exacerbated respiratory disease, severe liver or heart dysfunction)
* Women taking low-dose aspirin regularly before pregnancy (except ART indication)
* Age \<18 years
* Poor understanding of the French language
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

INSERM, Epopé team

UNKNOWN

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Catherine DENEUX, MD, PhD

Role: STUDY_DIRECTOR

Institut National de la Santé Et de la Recherche Médicale, France

Locations

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CHU Angers

Angers, , France

Site Status RECRUITING

CHU de Bordeaux

Bordeaux, , France

Site Status RECRUITING

Hôpital Femme Mère Enfant

Bron, , France

Site Status RECRUITING

Hôpital Antoine Béclère

Clamart, , France

Site Status RECRUITING

CHU Estaing

Clermont-Ferrand, , France

Site Status RECRUITING

Hôpital Intercommunal Créteil

Créteil, , France

Site Status RECRUITING

CHU Dijon Bourgogne

Dijon, , France

Site Status RECRUITING

CHU Lille

Lille, , France

Site Status RECRUITING

Hôpital de la conception et de la Timone

Marseille, , France

Site Status RECRUITING

Hôpital Nord

Marseille, , France

Site Status RECRUITING

CHRU de Nancy

Nancy, , France

Site Status RECRUITING

Hôpital Femme - Maternité

Nantes, , France

Site Status RECRUITING

Hôpital Armand Trousseau

Paris, , France

Site Status RECRUITING

Hôpital Cochin (site Port-Royal)

Paris, , France

Site Status RECRUITING

Hôpital Saint-Joseph

Paris, , France

Site Status RECRUITING

CHI de Poissy

Poissy, , France

Site Status RECRUITING

Hôpital Sud Rennes

Rennes, , France

Site Status RECRUITING

CHU Charles Nicolle

Rouen, , France

Site Status RECRUITING

CHU Strasbourg, CMCO Schiltigheim

Strasbourg, , France

Site Status RECRUITING

Hôpital de Hautepierre

Strasbourg, , France

Site Status RECRUITING

Hôpital Paule de Viguier

Toulouse, , France

Site Status RECRUITING

Hôpital Bretonneau

Tours, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Vassilis TSATSARIS, MD, PhD

Role: CONTACT

01 58 41 38 71

Alice CAMARA, MSc

Role: CONTACT

01 58 41 12 11

Facility Contacts

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Guillaume LEGENDRE

Role: primary

Loïc SENTILHES, Pr

Role: primary

Anthony ATTALAH, Dr

Role: primary

Alexandra LETOURNEAU, Dr

Role: primary

Denis GALOT, Dr

Role: primary

Edouard LECARPENTIER, Dr

Role: primary

Emmanuel SIMON, Dr

Role: primary

[email protected]

Role: backup

Louise GHESQUIERE, PhD

Role: primary

Florence BRETELLE, Pr

Role: primary

Julie BLANC, Dr

Role: primary

Olivier MOREL, MD, PhD

Role: primary

Norber WINER, Pr

Role: primary

Gilles KAYEM, Pr

Role: primary

Vassilis TSATSARIS, Pr

Role: primary

Elie AZRIA, Pr

Role: primary

Paul BERVEILLER, Pr

Role: primary

Maela LELOUS, Dr

Role: primary

Eric VERSPYCK, Pr

Role: primary

AS WEINGERTNER, Dr

Role: primary

Anne-Sophie WEINGERTNER, Dr

Role: primary

Paul GUERBY, Dr

Role: primary

Franck PERROTIN, Pr

Role: primary

Other Identifiers

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2022-A00374-39

Identifier Type: OTHER

Identifier Source: secondary_id

APHP211047

Identifier Type: -

Identifier Source: org_study_id

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