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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Low Molecular Weight Heparin, Enoxaparin, to Prevent Adverse Maternal and Perinatal Outcomes in Women With Previous Severe Preeclampsia at Less Than 34 Weeks' Gestation. A Prospective Randomized Trial

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) .


Detailed Summary:

  1. Purpose of the study: To determine whether low molecular weight heparin (LMWH) enoxaparin decreases the rate of maternal and perinatal composite morbidity in women who previously had a severe preeclampsia that occurred at less than 34 weeks' gestation.

  2. Patients and methods: Multicenter, prospective, randomized trial comparing 2 groups of patients:

    • First group treated with aspirin 100 mg/day until 35 weeks' gestation and enoxaparin subcutaneous 4000 UI/day until delivery.
    • Second group treated with aspirin 100 mg/day alone until 35 weeks' gestation.

    At first prenatal visit between 7-13 weeks, inclusion and exclusion criteria will be searched. Randomization will be performed by internet software. It will be performed by center.

    After randomization at first prenatal visit patients will be allocated to aspirin-enoxaparin or aspirin alone as mentioned above. Enoxaparin will be stopped the day of delivery or after the occurrence of a complication that necessitates delivery. Pregnancy management will be performed as recommended by standard care. Each month, blood samples will be drawn for platelets count and the analysis of angiogenic factors (sFlt1, sEng, free PlGF and VEGF). In addition, blood sample will be drawn at first prenatal visit for thrombophilia work-up (Prot C, Factor V Leiden, Prothrombin gene polymorphism). Only results of platelet count will be given to local investigators during the study. All other analysis will be performed at the end of the study by Pr Gris at NIMES, and will be blinded to clinical results.

  3. Same as current

    Current Secondary Outcome:

    • Recurrence of preeclampsia alone [ Time Frame: from randomization until one month after the delivery ]
    • Recurrence of severe preeclampsia [ Time Frame: from randomization until one month after the delivery ]
    • Fetal growth restriction alone [ Time Frame: from randomization until one month after the delivery ]
    • Severe fetal growth restriction (< 5th percentile) [ Time Frame: from randomization until one month after the delivery ]
    • Perinatal death alone [ Time Frame: from randomization until one month after the delivery ]
    • Neonatal death [ Time Frame: from randomization until one month after the delivery ]
    • Abruption alone [ Time Frame: from randomization until one month after the delivery ]
    • Maternal death [ Time Frame: from randomization until one month after the delivery ]
    • Fetal loss (10-21 weeks) [ Time Frame: from randomization until one month after the delivery ]
    • Fetal death [ Time Frame: from 15 weeks to delivery ]
    • Recurrence of preeclampsia controlled for thrombophilia analysis (polymorphism of factor V Leiden, prothrombin G20210A gene polymorphism) [ Time Frame: from randomization until one month after the delivery ]
    • Recurrence of preeclampsia controlled for angiogenic factors (free VEGF and PlGF, sFlt1, sEng) [ Time Frame: from randomization until one month after the delivery ]
    • Neonatal morbidity (NICU transfer, length of hospitalization, mechanical ventilation > 24 hours, respiratory distress syndrome, necrotizing enterocolitis, periventricular leucomalacia, bronchopulmonary dysplasia, intraventricular hemorrhage grade III-IV) [ Time Frame: from randomization until one month after the delivery ]
    • Enoxaparin toxicity: hemorrhage, skin reaction, thrombocytopenia (<100000/µL) related to heparin [ Time Frame: from randomization until one month after the delivery ]
    • Bone fracture [ Time Frame: from randomization until one month after the delivery ]


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: September 29, 2009
    Date Started: June 2009
    Date Completion:
    Last Updated: January 16, 2016
    Last Verified: January 2016