Prevention of Maternal and Perinatal Complications by Enoxaparin in Women With Previous Severe Preeclampsia - Full Text View

Purpose

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) .

Condition	Intervention	Phase
Preeclampsia	Drug: Lovenox® (enoxaparin) Drug: Aspegic ® (Aspirin)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
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

Resource links provided by NLM:

Genetics Home Reference related topics: preeclampsia

MedlinePlus related topics: Blood Thinners

Drug Information available for: Aspirin Enoxaparin sodium

Genetic and Rare Diseases Information Center resources: Eclampsia

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

The primary outcome is a composite morbidity that may occur : maternal death, or perinatal death, or preeclampsia, or abruptio placenta, or fetal growth restriction. [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Recurrence of preeclampsia alone [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Recurrence of severe preeclampsia [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Fetal growth restriction alone [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Severe fetal growth restriction (< 5th percentile) [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Perinatal death alone [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Neonatal death [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Abruption alone [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Maternal death [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Fetal loss (10-21 weeks) [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
Fetal death [ Time Frame: from 15 weeks to delivery ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Recurrence of preeclampsia controlled for angiogenic factors (free VEGF and PlGF, sFlt1, sEng) [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Enoxaparin toxicity: hemorrhage, skin reaction, thrombocytopenia (<100000/µL) related to heparin [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: Yes ]
Bone fracture [ Time Frame: from randomization until one month after the delivery ] [ Designated as safety issue: No ]


Enrollment:	257
Study Start Date:	June 2009
Study Completion Date:	November 2015
Primary Completion Date:	November 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lovenox® , 4000 UI/day (+ Aspegic®) Lovenox® (enoxaparin), 4000 UI/day (+ Aspegic® (Aspirin), 100 mg)	Drug: Lovenox® (enoxaparin) Injectable solution 4000 UI
Active Comparator: Aspegic ®, 100 mg/day Aspegic® (Aspirin),100 mg/day	Drug: Aspegic ® (Aspirin) 100 mg/day

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Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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
Antecedent of osteoporosis
Inability to do subcutaneous injection of heparin
Weight > 100 kg
Patient included in another interventional trial
Patient positive for anti-phospholipids antibodies
Patient positive for HIV or HCV or HBS

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00986765

Locations


France
Centre Hospitalier Intercommunal de Créteil
Creteil, France

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators


Principal Investigator:	Bassam Haddad	Assistance Publique - Hôpitaux de Paris

More Information


Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00986765 History of Changes
Other Study ID Numbers:	P071211
Study First Received:	September 29, 2009
Last Updated:	January 16, 2016
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:


Fetal growth restriction Abruptio placentae Perinatal death

Additional relevant MeSH terms:


Pre-Eclampsia Hypertension, Pregnancy-Induced Pregnancy Complications Aspirin Acetylsalicylic acid lysinate Heparin, Low-Molecular-Weight Enoxaparin Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents	Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics Anticoagulants

ClinicalTrials.gov processed this record on September 23, 2016

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