Clinical trial NCT05625724: Aspirin for the Prevention of Preeclampsia and Pregnancy Outcomes After Assisted Reproductive Technology
Official title: Aspirin for the Prevention of Preeclampsia and Pregnancy Outcomes in Nulliparous Women After Assisted Reproductive Technology. APPART
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: ART
Pre-Eclampsia
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2022-11-23
Enrollment: 1164
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo in the prevention of preterm (<37 weeks of gestation) preeclampsia
timeFrame: Up to 9 months
Secondary outcomes:
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on spontaneous and total preterm birth <34 weeks of gestation
timeFrame: Up to 8 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on spontaneous and total preterm birth <37 weeks of gestation
timeFrame: Up to 9 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of preeclampsia <34 weeks of gestation, term preeclampsia (≥ 37 weeks of gestation)
timeFrame: Up to 8 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of cesarean delivery
timeFrame: Up to 9 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of postpartum hemorrhage (>500ml)
timeFrame: Up to 9 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of placental abruption
timeFrame: Up to 9 months
measure: Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on neonatal adverse outcome.
timeFrame: Up to 9 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Dijon
country: France
facility: CHU Dijon-Bourgogne
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: HCL - Groupement Hospitalier Est, Hôpital Femme Mère Enfant
city: Marseille
country: France
facility: AP-HM Hôpital de la Conception
city: Marseille
country: France
facility: AP-HM Hôpital Nord
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHRU Nancy
city: Nantes
country: France
facility: CHU Nantes
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: Groupe hospitalier St Joseph
city: Paris
country: France
facility: Hôpital Armand - Trousseau
city: Paris
country: France
facility: Hôpital Cochin
city: Poissy
country: France
facility: CHI Poissy Saint Germain en Laye
city: Poitiers
country: France
facility: CHU Poitiers
city: Rennes
country: France
facility: CHU Rennes
city: Saint-Étienne
country: France
facility: CHU Saint Etienne, Hôpital Nord
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: University Hospital, Toulouse
name: Christophe VAYSSIERE, MD
role: PRINCIPAL_INVESTIGATOR
References: