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

Pre-Eclampsia Clinical Trial

— APPART  

Official title:

Aspirin for the Prevention of Preeclampsia and Pregnancy Outcomes in Nulliparous Women After Assisted Reproductive Technology. APPART

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05625724
• Other study ID #: RC31/21/0337
• Status: Recruiting
• Phase: Phase 3
• Start date: August 2, 2023
• Est. completion date: May 2026

Study information

• Verified date: January 2024
• Source: University Hospital, Toulouse
• Contact: Paul GUERBY, MD
• Phone: 5 67 77 12 33
• Email: guerby.p[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 1164
• Est. completion date: May 2026
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ART
• Eclampsia
• Pre-Eclampsia

Intervention

Drug:
• Aspirin
Experimental drug administrated orally
• Placebo
Treatment for the control group

Locations

Country	Name	City	State
France	CHU Angers	Angers
France	CHU Bordeaux	Bordeaux
France	CHU Clermont-Ferrand	Clermont-Ferrand
France	CHU Dijon-Bourgogne	Dijon
France	CHU Lille	Lille
France	HCL - Groupement Hospitalier Est, Hôpital Femme Mère Enfant	Lyon
France	AP-HM Hôpital de la Conception	Marseille
France	AP-HM Hôpital Nord	Marseille
France	CHU Montpellier	Montpellier
France	CHRU Nancy	Nancy
France	CHU Nantes	Nantes
France	CHU Nîmes	Nîmes
France	Groupe hospitalier St Joseph	Paris
France	Hôpital Armand - Trousseau	Paris
France	Hôpital Cochin	Paris
France	CHI Poissy Saint Germain en Laye	Poissy
France	CHU Poitiers	Poitiers
France	CHU Rennes	Rennes
France	CHU Saint Etienne, Hôpital Nord	Saint-Étienne
France	CHU Strasbourg	Strasbourg
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Occurrence of preterm (<37 weeks of gestation) preeclampsia (binary variable yes/no)	Up to 9 months
Secondary	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	Occurrence of spontaneous and total preterm birth (defined by delivery at <34 weeks of gestation)	Up to 8 months
Secondary	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	Occurrence of spontaneous and total preterm birth (defined by delivery at <37weeks of gestation)	Up to 9 months
Secondary	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)	Occurrence of term (=37 weeks) preeclampsia	Up to 8 months
Secondary	Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of cesarean delivery	Occurrence of cesarean delivery	Up to 9 months
Secondary	Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of postpartum hemorrhage (>500ml)	Occurrence of postpartum hemorrhage (>500ml)	Up to 9 months
Secondary	Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on occurrence of placental abruption	Occurrence of placental abruption	Up to 9 months
Secondary	Compare the effect of aspirin 150mg daily initiated between 9 and 14 weeks of gestation versus placebo on neonatal adverse outcome.	Occurrence of neonatal adverse outcomes: still birth, neonatal death, neonatal complications	Up to 9 months