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

NCT ID: NCT01051778

Last Updated: 2011-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30
• Study Completion Date: 2009-12-31

Brief Summary

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

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).

Conditions

Recurrent Abortion

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

enoxaparin 40 mg plus low dose aspirin

Group Type: EXPERIMENTAL

enoxaparin 40mg plus low dose aspirin

Intervention Type: DRUG

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.

Heparin calcium 5,000 U twice daily plus low dose aspirin

Group Type: ACTIVE_COMPARATOR

Heparin calcium5,000 U twice daily plus low dose aspirin

Intervention Type: DRUG

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 .

Interventions

enoxaparin 40mg plus low dose aspirin

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.

Intervention Type: DRUG

Heparin calcium5,000 U twice daily plus low dose aspirin

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 .

Intervention Type: DRUG

Other Intervention Names

Clexane 40 mg; Cal-Heparine

Eligibility Criteria

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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 37 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Ahmed Elgazzar Hospital

OTHER

Sponsor Role: collaborator

Cairo University

OTHER

Sponsor Role: lead

Responsible Party

Cairo university

Principal Investigators

Usama M Fouda

Role: PRINCIPAL_INVESTIGATOR

Lecturer of obstetrics and Gynecology , Cairo university

Ahmed M Sayed

Role: PRINCIPAL_INVESTIGATOR

Assistant professor of obstetrics and Gynecology , Cairo university.

Locations

Ahmed Elgazzar hospital

Cairo, , Egypt

Cairo university hospital

Cairo, , Egypt

Countries

Egypt

References

Noble LS, Kutteh WH, Lashey N, Franklin RD, Herrada J. Antiphospholipid antibodies associated with recurrent pregnancy loss: prospective, multicenter, controlled pilot study comparing treatment with low-molecular-weight heparin versus unfractionated heparin. Fertil Steril. 2005 Mar;83(3):684-90. doi: 10.1016/j.fertnstert.2004.11.002.

Reference Type: BACKGROUND

PMID: 15749498 (View on PubMed)

Stephenson MD, Ballem PJ, Tsang P, Purkiss S, Ensworth S, Houlihan E, Ensom MH. Treatment of antiphospholipid antibody syndrome (APS) in pregnancy: a randomized pilot trial comparing low molecular weight heparin to unfractionated heparin. J Obstet Gynaecol Can. 2004 Aug;26(8):729-34. doi: 10.1016/s1701-2163(16)30644-2.

Reference Type: BACKGROUND

PMID: 15307977 (View on PubMed)

Hamulyak EN, Scheres LJ, Marijnen MC, Goddijn M, Middeldorp S. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020 May 2;5(5):CD012852. doi: 10.1002/14651858.CD012852.pub2.

Reference Type: DERIVED

PMID: 32358837 (View on PubMed)

Fouda UM, Sayed AM, Abdou AM, Ramadan DI, Fouda IM, Zaki MM. Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome. Int J Gynaecol Obstet. 2011 Mar;112(3):211-5. doi: 10.1016/j.ijgo.2010.09.010. Epub 2011 Jan 19.

Reference Type: DERIVED

PMID: 21251653 (View on PubMed)

Other Identifiers

Aps/UFH/enox40

Identifier Type: -

Identifier Source: org_study_id