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

Recurrent Abortion Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01051778
• Other study ID #: Aps/UFH/enox40
• Status: Completed
• Phase: Phase 2
• First received: January 19, 2010
• Last updated: July 29, 2011
• Start date: June 2006
• Est. completion date: December 2009

Study information

• Verified date: January 2010
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 37 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Abortion, Habitual
• Antiphospholipid Syndrome
• Recurrent Abortion

Intervention

Drug:
• 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.
• 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 .

Locations

Country	Name	City	State
Egypt	Ahmed Elgazzar hospital	Cairo
Egypt	Cairo university hospital	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Cairo University	Ahmed Elgazzar Hospital

Country where clinical trial is conducted

Egypt, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Minor and Major Bleeding		Duration of pregnancy and puerperium	Yes
Secondary	Thrombocytopenia		Duration of pregnancy and puerperium	Yes
Secondary	Preeclampsia		Pregnancy > 20 weeks gestation	Yes
Secondary	IUFD		Pregnancy >24 weeks gestation	No
Secondary	Preterm Delivery		24 weeks gestation<Pregnancy <37weeks gestation	No
Secondary	Spontaneous Osteoporotic Fractures		Duration of pregnancy and puerperium	Yes