Aspirin for the Prevention of Preeclampsia and Pregnancy Outcomes After Assisted Reproductive Technology

NCT ID: NCT05625724

Last Updated: 2024-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1164 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-02
• Study Completion Date: 2026-05-31

Brief Summary

This study seeks to validate the hypothesis that nulliparous pregnant women after Assisted Reproductive Technology (ART) are at high risk of preeclampsia and perinatal complications and represent a subgroup for which aspirin prophylaxis during pregnancy may be effective in the prevention of preterm preeclampsia and other perinatal adverse outcomes.

Detailed Description

Preeclampsia (PE) affects 2% of pregnancies in France and is an important cause of maternal and perinatal mortality and morbidity. Aspirin is currently the only prophylactic therapy for PE in high-risk women when initiated before 16 weeks of gestation and at a daily dose of 100-160 mg, with a reduction in the incidence of preterm preeclampsia of 60-70% in recent meta-analysis. Latest data also demonstrate a potential beneficial effect of aspirin on spontaneous preterm birth. A major challenge in modern obstetrics is early identification of pregnant women at high-risk of PE who could benefit from aspirin treatment. In France, the College National des Gynécologues et Obstétriciens Français and the Société Française d'HyperTension Artérielle have restrictive recommendation of aspirin to be prescribed only to women with a history of PE or vascular intra-uterine growth restriction, thus leaving out all nulliparous women (including those with multiple risk factors). Other countries (USA, United Kingdom (UK), Canada) have much broader recommendations with aspirin prescription for patients with one high or 2 moderate risk factors, but exposing nearly 30% of pregnant women to aspirin (leading to unnecessary exposure to treatment). The Fetal Medicine Foundation provides a screening test combining clinical parameters, uterine artery Doppler, and biomarkers; but this strategy has high false-positive rate and the reproducibility needs to be confirmed in clinical practice.

It seems necessary to be able to better target women at risk, especially in nulliparous women. Nulliparity and assisted reproductive technology (ART) are independent risk factors for PE. Currently the proportion of pregnancy after ART in France is roughly 6.9% and is rising. Nulliparous ART pregnant women have a higher risk of PE and preterm birth. Indeed, they commonly cumulate risk factors including age>35years in association with nulliparity and ART. The rate of PE in this population can rise up to 10%.

Our hypothesis is that nulliparous pregnant women after ART are at high risk of preeclampsia and perinatal complications and represent a subgroup for which aspirin prophylaxis during pregnancy may be effective in the prevention of preterm preeclampsia and other perinatal adverse outcomes.

Conditions

ART; Pre-Eclampsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Aspirin

Low-dose Aspirin: 150mg, daily, oral route, at bedtime, initiated between 9 and 14 weeks of gestation, until 35 (+6) weeks of gestation, or in the event of earlier delivery, until the onset of labor.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

Experimental drug administrated orally

Control

Matching placebo administrated daily, oral route, at bedtime, initiated between 9 and 14 weeks of gestation, until 35 (+6) weeks of gestation, or in the event of earlier delivery, until the onset of labor.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Treatment for the control group

Interventions

Aspirin

Experimental drug administrated orally

Intervention Type: DRUG

Placebo

Treatment for the control group

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Nulliparous women aged 18 years or more
• Pregnancy following ART, including in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), oocyte donation or intrauterine insemination with sperm donor
• Singleton pregnancy
• Evolutive pregnancy between 9 and 14 weeks of gestation
• Women affiliated to a French Social Security Insurance or equivalent social protection
• Written informed consent

Exclusion Criteria

• Major fetal abnormality
• Regular treatment with aspirin (including antiphospholipid syndrome)
• Aspirin contraindications (allergy, von Willebrand disease, peptic ulceration, hemophilia)
• Women protected by law.
• Women included in another interventional study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe VAYSSIERE, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

CHU Angers

Angers, , France

Site Status: RECRUITING

CHU Bordeaux

Bordeaux, , France

Site Status: RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

CHU Dijon-Bourgogne

Dijon, , France

Site Status: RECRUITING

CHU Lille

Lille, , France

Site Status: RECRUITING

HCL - Groupement Hospitalier Est, Hôpital Femme Mère Enfant

Lyon, , France

Site Status: RECRUITING

AP-HM Hôpital de la Conception

Marseille, , France

Site Status: RECRUITING

AP-HM Hôpital Nord

Marseille, , France

Site Status: RECRUITING

CHU Montpellier

Montpellier, , France

Site Status: RECRUITING

CHRU Nancy

Nancy, , France

Site Status: RECRUITING

CHU Nantes

Nantes, , France

Site Status: RECRUITING

CHU Nîmes

Nîmes, , France

Site Status: RECRUITING

Groupe hospitalier St Joseph

Paris, , France

Site Status: RECRUITING

Hôpital Armand - Trousseau

Paris, , France

Site Status: NOT_YET_RECRUITING

Hôpital Cochin

Paris, , France

Site Status: RECRUITING

CHI Poissy Saint Germain en Laye

Poissy, , France

Site Status: RECRUITING

CHU Poitiers

Poitiers, , France

Site Status: NOT_YET_RECRUITING

CHU Rennes

Rennes, , France

Site Status: RECRUITING

CHU Saint Etienne, Hôpital Nord

Saint-Etienne, , France

Site Status: RECRUITING

CHU Strasbourg

Strasbourg, , France

Site Status: RECRUITING

CHU Toulouse

Toulouse, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Paul GUERBY, MD

Role: CONTACT

guerby.p@chu-toulouse.fr

5 67 77 12 33

Delphine DUCHANOIS, Midwife

Role: CONTACT

duchanois.d@chu-toulouse.fr

5 67 77 12 33 ext. +33

Facility Contacts

Pierre-Emmanuel BOUET, MD

Role: primary

Loic Sentilhes, MD

Role: primary

Amélie DELABAERE, MD

Role: primary

Emmanuel Simon, MD

Role: primary

Véronique Debarge, MD

Role: primary

Mona Massoud, MD

Role: primary

Blandine Courbière, MD

Role: primary

Julie Blanc, MD

Role: primary

Noémie Ranisavljevic, MD

Role: primary

Catherine Zuili Lamy, MD

Role: primary

Vincent Dochez, MD

Role: primary

Stéphanie Huberlant, MD

Role: primary

Elie Azria, MD

Role: primary

Gilles Kayem, MD

Role: primary

Vassilis Tsatsaris, MD

Role: primary

Paul Berveiller, MD

Role: primary

Aurélie Brossard Violeau, MD

Role: primary

Céline Pimentel, MD

Role: primary

Tiphaine Barjat, MD

Role: primary

Catherine Rongières, MD

Role: primary

Paul GUERBY, MD

Role: primary

guerby.p@chu-toulouse.fr

Other Identifiers

RC31/21/0337

Identifier Type: -

Identifier Source: org_study_id