Low-molecular-weight Heparin (LMWH) Versus Unfractionated Heparin (UFH) in Pregnant Women With Recurrent Abortion Secondary to Antiphospholipid Syndrome

Study Overview
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Brief Summary
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The aim of this study is to compare the efficacy and safety of Low molecular weight heparin (LMWH) plus low dose aspirin (LDA) with unfractionated heparin(UFH) plus LDA in women with recurrent pregnancy loss associated with antiphospholipid syndrome (APS).

Detailed Description
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Women with antiphospholipid syndrome (APS) have live birth rates as low as 10% in pregnancies without pharmacological treatment. Low dose aspirin (LDA) ,unfractionated heparin(UFH) , Low molecular weight heparin (LMWH) , prednisone, and intravenous immunoglobulin (IVIG) have been used either alone or in combination in order to improve the live birth rate in APS positive women with recurrent miscarriage. A Cochrane review of 13 randomized or quasi-randomized, controlled trials of various management options of pregnant women with a history of pregnancy loss and APL, revealed that combined UFH and aspirin was the treatment of choice which reduced pregnancy loss by 54% . During the past decade , low molecular weight heparins were widely used in the prophylaxis and treatment of patients with venous or arterial thrombosis ,with an efficacy and safety superior or at least equivalent to that of UFH .Although recent studies reported the use of LMWH in the management of patients recurrent pregnancy loss secondary to antiphospholipid syndrome resulted in encouraging results . It is not clear whether the efficacy and safety of LMWH is equivalent to that of UFH . Although LMWH is more expensive than UFH . LMWH has longer half life , greater bioavailability , more stable dose-response relationship than UFH and therefore can be administered once daily. Furthermore, LMWH requires less frequent monitoring than UFH and and has less adverse effect on bone mineral density and platelet count .These advantages make LMWH more attractive for the patients and physicians than UFH . There are only two studies which compared the efficacy of LMWH plus LDA with that of UFH plus LDA in the management of pregnant women with recurrent pregnancy loss secondary to APS. In addition ,no randomized controlled study has yet compared the efficacy of LMWH plus LDA with UFH plus LDA. The aim of this study is to compare the efficacy and safety of Low molecular weight heparin (LMWH) plus low dose aspirin (LDA) with unfractionated heparin(UFH) plus LDA in women with recurrent pregnancy loss associated with antiphospholipid syndrome (APS).

Official Title
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Low-molecular-weight Heparin Versus Unfractionated Heparin in Pregnant Women With History of Recurrent Abortion Secondary to Antiphospholipid Syndrome. A Randomized Controlled Trial

Conditions
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Recurrent Abortion

Intervention / Treatment
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* Drug: enoxaparin 40mg plus low dose aspirin
* Drug: Heparin calcium5,000 U twice daily plus low dose aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a minimum of three consecutive pregnancy losses before 10 weeks gestation Positive lupus anticoagulant and/or anticardiolipin antibodies (IgG and IgM) on at least two occasions twelve weeks apart . Age between 19 - 37 years, Body mass index between 19-30 Exclusion Criteria: Parental chromosomal abnormalities Uterine abnormalities Luteal phase defect Systemic lupus erythematosus Previous thromboembolism Sensitivity to aspirin.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: enoxaparin 40 mg plus low dose aspirin<br> | Drug: enoxaparin 40mg plus low dose aspirin<br>* Enoxaparin 40mg/day by subcutaneous injection ( Clexane 40 mg, Aventis international, Sanofi-aventis France ) is started when the serum pregnancy test become positive. Enoxaparin is stopped 2 days before planned induction of labor or cesarean section and twice-daily unfractionated heparin (UFH) is initiated. The evening UFH dose is cancelled before planned caesarean section . The patients are asked to stop enoxaparin or UFH with the beginning of labor pains . Low dose aspirin (75 mg/day)(Aspocid Paediatric ,Chemical Industries Development (CID)) is started before conception and continued until 36 weeks gestation.<br>* Other names: Clexane 40 mg;|
| Active Comparator: Heparin calcium 5,000 U twice daily plus low dose aspirin<br> | Drug: Heparin calcium5,000 U twice daily plus low dose aspirin<br>* Heparin Calcium 5,000 U twice daily (Cal-Heparine, Amoun Pharmaceutical Co, Egypt) by subcutaneous injection is started when the serum pregnancy test become positive. The evening UFH dose is cancelled before planned caesarean section . The patients are asked to stop UFH with the beginning of labor pains . Low dose aspirin (75 mg/day)(Aspocid Paediatric ,Chemical Industries Development (CID))is started before conception and continued until 36 weeks gestation .<br>* Other names: Cal-Heparine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth Rate = (Number of Live Births / Total Number of Pregnancies) | Live birth occurs when a fetus (> 24 weeks ) , exits the maternal body and subsequently shows signs of life, such as voluntary movement, heartbeat, or pulsation of the umbilical cord. | pregnancy > 24weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minor and Major Bleeding |  | Duration of pregnancy and puerperium | 
| Thrombocytopenia |  | Duration of pregnancy and puerperium | 
| Preeclampsia |  | Pregnancy > 20 weeks gestation | 
| IUFD |  | Pregnancy >24 weeks gestation | 
| Preterm Delivery |  | 24 weeks gestation<Pregnancy <37weeks gestation | 
| Spontaneous Osteoporotic Fractures |  | Duration of pregnancy and puerperium | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Recurrent abortion, Antiphospholipid syndrome, unfractionated heparin, Low Molecular Weight Heparin