Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers

NCT01729468 | Completed Phase 4 DMC

• 5 other identifiers: PHRN08-FP/PERASTUN2011-003536-302012-R8A120316-72912140
• Study Type: interventional
• Target: 1,106
• Locations: 2 countries
• Sites: 17

Brief Summary

The objective of this study is to test the efficacy of low-dose aspirin (160 mg/day), given bedtime and started early during pregnancy (≤ 15 +6 weeks of gestation) in nulliparous pregnant women selected as "high-risk" by the presence of a bilateral uterine artery notch and/or bilateral uterine artery PI ≥ 1.7 during the first trimester ultrasound scan (11-13+6 weeks), to prevent the occurrence of pre-eclampsia or small for gestational age at birth.

Conditions

Pre-eclampsia; Intra-uterine Growth Restriction

Keywords

Low Dose Acetylsalicylic Acid; Prevention; Pre-eclampsia; Intra-uterine Growth Restriction; Primiparous Women; Bilateral Uterine Artery Notches; First Quarter

Outcome Measures

Primary Outcomes (1)

• Preeclampsia (diagnosed per ACOG criteria) and small for gestational age at birth (≤5th percentile on customized growth curves)

  women will be followed for the duration of pregnancy and postpartum, an expected average of 26 to 31 weeks

Secondary Outcomes (6)

• Small for gestational age at birth (≤5th percentile on customized growth curves)

  women will be followed for the duration of pregnancy, an expected average of 25 to 30 weeks

• Pre-eclampsia (ACOG criteria) requiring delivery before 34 weeks

  women will be followed for the duration of pregnancy and postpartum, an expected average of 26 to 31 weeks

• Severe pre-eclampsia (ACOG criteria)

  women will be followed for the duration of pregnancy and postpartum, an expected average of 26 to 31 weeks

• Perinatal death (22 weeks of gestation to 7 days postnatal)

  women will be followed for the duration of pregnancy and postpartum, an expected average of 26 to 31 weeks

• Pre-eclampsia (ACOG criteria)

  women will be followed for the duration of pregnancy and postpartum, an expected average of 26 to 31 weeks

Other Outcomes (2)

• Mode of delivery (vaginal or cesarean)

  women will be followed for the duration of pregnancy, an expected average of 25 to 30 weeks

• Mode of anesthesia for delivery

  women will be followed for the duration of pregnancy, an expected average of 25 to 30 weeks

Study Arms (2)

Aspirin

EXPERIMENTAL

Aspirin 160 mg per day

Drug: Aspirin

Placebo

PLACEBO COMPARATOR

Placebo 160 mg per day

Drug: Placebo

Interventions

Aspirin DRUG

Aspirin, 160 mg per day until 34 weeks of gestation

Aspirin

Placebo DRUG

Placebo, 160 mg per day until 34 weeks of gestation

Placebo

Eligibility Criteria

• Age: 18 Months+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Nulliparous (no previous pregnancy ≥ 22 SA)
• Singleton pregnancy
• Gestational age ≤ 15 +6 weeks
• Bilateral uterine artery notch (grade ≥ 2) and/or bilateral uterine artery PI ≥ 1.7 during first trimester ultrasound (CRL between 45 and 84 mm)
• Maternal informed consent obtained
• Affiliated to social security system

You may not qualify if:

• Women considering voluntary pregnancy termination (≤ 14 weeks)
• Pre-existing (maternal) indication for premature delivery before 37 weeks
• Fetal condition detected during the first trimester scan (fetal malformation or nuchal translucency ≥ 95th percentile)
• Women under anticoagulation
• Allergy or hypersensitivity to Kardegic® or one of its constituents
• Secondary hemostasis disorder responsible for bleeding or risk of bleeding
• Peptic ulcer under evolution
• Lupus or antiphospholipid syndrome

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (17)

Service de Gynécologie-Obstétrique, Groupe Hospitalier Pellegrin, CHRU de Bordeaux

Bordeaux, 33000, France

Location

Service de Gynécologie-Obstétrique, HFME, Hospices Civils de Lyon

Bron, 69677, France

Location

Service de gynécologie-obstétrique, Polyclinique du PARC

Caen, 14052, France

Location

Service de Gynécologie-Obstétrique, Hôpital d'Estaing, CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Service de gynécologie-obstétrique, Hôpital Couple Enfant, CHRU de Grenoble

Grenoble, 38043, France

Location

Cabinet Mosaïque Santé

La Chaussée-Saint-Victor, 41260, France

Location

Service de gynécologie-obstétrique, CHR Le Mans

Le Mans, 72037, France

Location

Service de Gyénécologie-Obstétrique, Hôpital Jeanne de Flandre, CHRU de Lille

Lille, 59037, France

Location

Service de Gynécologie-Obstétrique, Hôpital Arnaud de Villeneuve, CHRU de Montpellier

Montpellier, 34295, France

Location

Service de gynécologie-obstétrique, Hôpital Mère-Enfant, CHRU de Nantes

Nantes, 44093, France

Location

Service de gynécologie-obstétrique, Polyclinique de l'Atlantique

Nantes, 44819, France

Location

Service de Gynécologie-Obstétrique, Hôpital Carémeau, CHRU de Nîmes

Nîmes, 30029, France

Location

Service de Gynécologie-Obstétrique, Hôpital Porte Madeleine, CHR d'Orléans

Orléans, 45032, France

Location

Centre de dépistage PRIMA FACIE, Hôpital Necker, APHP

Paris, 75014, France

Location

Service de Gynécologie-Obstétrique, Hôpital Paule de Viguier, CHU de Toulouse

Toulouse, 31059, France

Location

Service de Gynécologie-Obstetrique, Centre Olympe de Gouges, CHRU de Tours

Tours, 37044, France

Location

Service de gynécologie-obstétrique, Maison de la Femme de la Mère et de l'Enfant, CHU de Fort de France

Fort-de-France, 97261, Martinique

Location

Related Publications (4)

• Poon LC, Syngelaki A, Akolekar R, Lai J, Nicolaides KH. Combined screening for preeclampsia and small for gestational age at 11-13 weeks. Fetal Diagn Ther. 2013;33(1):16-27. doi: 10.1159/000341712. Epub 2012 Sep 13.

  PMID: 22986844 BACKGROUND

• Ayala DE, Ucieda R, Hermida RC. Chronotherapy with low-dose aspirin for prevention of complications in pregnancy. Chronobiol Int. 2013 Mar;30(1-2):260-79. doi: 10.3109/07420528.2012.717455. Epub 2012 Sep 24.

  PMID: 23004922 BACKGROUND

• Plasencia W, Maiz N, Poon L, Yu C, Nicolaides KH. Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol. 2008 Aug;32(2):138-46. doi: 10.1002/uog.5402.

  PMID: 18634131 BACKGROUND

• Diguisto C, Le Gouge A, Marchand MS, Megier P, Ville Y, Haddad G, Winer N, Arthuis C, Doret M, Debarge VH, Flandrin A, Delmas HL, Gallot D, Mares P, Vayssiere C, Sentilhes L, Cheve MT, Paumier A, Durin L, Schaub B, Equy V, Giraudeau B, Perrotin F; Groupe de Recherche en Obstetrique et Gynecologie (GROG). Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial. PLoS One. 2022 Oct 19;17(10):e0275129. doi: 10.1371/journal.pone.0275129. eCollection 2022.

  PMID: 36260615 RESULT

MeSH Terms

Conditions

Pre-Eclampsia

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Franck PERROTIN, MD-PhD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2012
• First Posted: November 20, 2012
• Study Start: June 27, 2012
• Primary Completion: October 25, 2016
• Study Completion: October 25, 2016
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

MA (1); FR (16)