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

Phase 3
Recruiting
Conditions
ART
Pre-Eclampsia
Interventions
Drug: Placebo
Registration Number
NCT05625724
Lead Sponsor
University Hospital, Toulouse
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
Female
Target Recruitment
1164
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlPlaceboMatching 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.
AspirinAspirinLow-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.
Primary Outcome Measures
NameTimeMethod
Effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo in the prevention of preterm (<37 weeks of gestation) preeclampsiaUp to 9 months

Occurrence of preterm (\<37 weeks of gestation) preeclampsia (binary variable yes/no)

Secondary Outcome Measures
NameTimeMethod
Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of cesarean deliveryUp to 9 months

Occurrence of cesarean delivery

Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of placental abruptionUp to 9 months

Occurrence of placental abruption

Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on neonatal adverse outcome.Up to 9 months

Occurrence of neonatal adverse outcomes: still birth, neonatal death, neonatal complications

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 gestationUp to 8 months

Occurrence of spontaneous and total preterm birth (defined by delivery at \<34 weeks of gestation)

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 gestationUp to 9 months

Occurrence of spontaneous and total preterm birth (defined by delivery at \<37weeks of gestation)

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)Up to 8 months

Occurrence of term (≥37 weeks) preeclampsia

Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of postpartum hemorrhage (>500ml)Up to 9 months

Occurrence of postpartum hemorrhage (\>500ml)

Trial Locations

Locations (21)

CHRU Nancy

🇫🇷

Nancy, France

Hôpital Armand - Trousseau

🇫🇷

Paris, France

CHU Bordeaux

🇫🇷

Bordeaux, France

CHU Clermont-Ferrand

🇫🇷

Clermont-Ferrand, France

CHU Angers

🇫🇷

Angers, France

CHU Dijon-Bourgogne

🇫🇷

Dijon, France

HCL - Groupement Hospitalier Est, Hôpital Femme Mère Enfant

🇫🇷

Lyon, France

CHU Lille

🇫🇷

Lille, France

AP-HM Hôpital Nord

🇫🇷

Marseille, France

CHU Montpellier

🇫🇷

Montpellier, France

Groupe hospitalier St Joseph

🇫🇷

Paris, France

CHI Poissy Saint Germain en Laye

🇫🇷

Poissy, France

CHU Toulouse

🇫🇷

Toulouse, France

CHU Saint Etienne, Hôpital Nord

🇫🇷

Saint-Étienne, France

CHU Strasbourg

🇫🇷

Strasbourg, France

AP-HM Hôpital de la Conception

🇫🇷

Marseille, France

CHU Nantes

🇫🇷

Nantes, France

CHU Poitiers

🇫🇷

Poitiers, France

CHU Rennes

🇫🇷

Rennes, France

CHU Nîmes

🇫🇷

Nîmes, France

Hôpital Cochin

🇫🇷

Paris, France

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