Prevention of Maternal and Perinatal Complications by Enoxaparin in Women With Previous Severe Preeclampsia

NCT00986765 | Completed Phase 3 DMC

• 1 other identifier: P071211
• Study Type: interventional
• Target: 257
• Locations: 1 country
• Sites: 1

Brief Summary

Preeclampsia (PE) complicates 2-8% of pregnancies. It is associated with an increased risk of adverse maternal (death, eclampsia, abruptio placenta, HELLP syndrome) and perinatal (perinatal death, growth restriction, prematurity) outcomes. The only definite treatment of PE remains pregnancy termination. Therefore, prevention of PE remains an important challenge. Low dose aspirin may be used in the prevention of PE, particularly in women who had a severe preeclampsia before 34 weeks. Its efficiency, however, is very weak. Recently, it has been suggested that low molecular weight heparin might be useful in the prevention of PE. The aim of this study is to analyze the usefulness of the enoxaparin 4000 UI/day in the prevention of a composite maternal or perinatal morbidity (occurrence of one of the following events: maternal death, PE, fetal growth retardation, abruptio placenta, perinatal death) in women who previously had a severe preeclampsia at less than 34 weeks' gestation. To answer this question, the investigators propose to conduct a multicenter prospective randomized trial that will compare two groups in parallel: a group where women will have an association of enoxaparin 4000 U/day and aspirin 100 mg/day and another group where women would have only aspirin 100 mg/day. The number of patients needed is 255 (amendment n°2-approved 06/12/2011) .

Conditions

Preeclampsia

Keywords

Fetal growth restriction; Abruptio placentae; Perinatal death

Outcome Measures

Primary Outcomes (1)

• The primary outcome is a composite morbidity that may occur : maternal death, or perinatal death, or preeclampsia, or abruptio placenta, or fetal growth restriction.

  from randomization until one month after the delivery

Secondary Outcomes (15)

• Recurrence of preeclampsia alone

  from randomization until one month after the delivery

• Recurrence of severe preeclampsia

  from randomization until one month after the delivery

• Fetal growth restriction alone

  from randomization until one month after the delivery

• Severe fetal growth restriction (< 5th percentile)

  from randomization until one month after the delivery

• Perinatal death alone

  from randomization until one month after the delivery

Study Arms (2)

Lovenox® , 4000 UI/day (+ Aspegic®)

EXPERIMENTAL

Lovenox® (enoxaparin), 4000 UI/day (+ Aspegic® (Aspirin), 100 mg)

Drug: Lovenox® (enoxaparin)

Aspegic ®, 100 mg/day

ACTIVE COMPARATOR

Aspegic® (Aspirin),100 mg/day

Drug: Aspegic ® (Aspirin)

Interventions

Lovenox® (enoxaparin) DRUG

Injectable solution 4000 UI

Lovenox® , 4000 UI/day (+ Aspegic®)

Aspegic ® (Aspirin) DRUG

100 mg/day

Aspegic ®, 100 mg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient ≥ 18 years
• Patient with a previous severe preeclampsia that occurred at less than 34 weeks' gestation
• Patient between 7 and 13 weeks +6 days at first prenatal visit
• Singleton pregnancy
• Affiliation to social security
• Informed consent given after receiving information on the study.

You may not qualify if:

• Patient under law protection
• Inability to sign written consent
• Inability to follow the protocol because of a psychiatric disease
• History of deep venous thromboembolism during previous pregnancy
• Need of low molecular weight heparin during pregnancy
• Previous arterial thrombosis
• Patient having a cardiac valvular prosthesis that necessitates anticoagulation during pregnancy
• Renal failure (creatinine clearance \< 30 ml/min, or serum creatinine \> 180 µmol/L
• Previous hemorrhagic disease
• A disease that might bleed (gastric ulcer)
• Antiphospholipid antibody syndrome
• Allergy to Aspirin
• Allergy to heparins
• Thrombocytopenia related to heparin use
• Thrombocytopenia \<100,000 /µL at first prenatal visit

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Location

Related Publications (3)

• Lecarpentier E, Gris JC, Cochery-Nouvellon E, Mercier E, Abbas H, Thadhani R, Karumanchi SA, Haddad B. Urinary Placental Growth Factor for Prediction of Placental Adverse Outcomes in High-Risk Pregnancies. Obstet Gynecol. 2019 Dec;134(6):1326-1332. doi: 10.1097/AOG.0000000000003547.

  PMID: 31764746 DERIVED

• Lecarpentier E, Gris JC, Cochery-Nouvellon E, Mercier E, Touboul C, Thadhani R, Karumanchi SA, Haddad B. Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis. Obstet Gynecol. 2018 Jan;131(1):63-69. doi: 10.1097/AOG.0000000000002380.

  PMID: 29215518 DERIVED

• Haddad B, Winer N, Chitrit Y, Houfflin-Debarge V, Chauleur C, Bages K, Tsatsaris V, Benachi A, Bretelle F, Gris JC, Bastuji-Garin S; Heparin-Preeclampsia (HEPEPE) Trial Investigators. Enoxaparin and Aspirin Compared With Aspirin Alone to Prevent Placenta-Mediated Pregnancy Complications: A Randomized Controlled Trial. Obstet Gynecol. 2016 Nov;128(5):1053-1063. doi: 10.1097/AOG.0000000000001673.

  PMID: 27741174 DERIVED

MeSH Terms

Conditions

Pre-Eclampsia; Fetal Growth Retardation; Abruptio Placentae; Perinatal Death

Interventions

Enoxaparin; acetylsalicylic acid lysinate; Aspirin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Fetal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor Complications; Placenta Diseases; Death

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Bassam Haddad

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2009
• First Posted: September 30, 2009
• Study Start: June 1, 2009
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

FR (1)