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

This study has been completed.
Sponsor:
Collaborator:
Ahmed Elgazzar Hospital
Information provided by:
Cairo University
ClinicalTrials.gov Identifier:
NCT01051778
First received: January 19, 2010
Last updated: July 29, 2011
Last verified: January 2010

January 19, 2010
July 29, 2011
June 2006
November 2009   (final data collection date for primary outcome measure)
Live Birth Rate = (Number of Live Births / Total Number of Pregnancies) [ Time Frame: pregnancy > 24weeks gestation ] [ Designated as safety issue: No ]
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.
Live birth rate [ Time Frame: pregnancy > 24weeks gestation ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01051778 on ClinicalTrials.gov Archive Site
  • Minor and Major Bleeding [ Time Frame: Duration of pregnancy and puerperium ] [ Designated as safety issue: Yes ]
  • Thrombocytopenia [ Time Frame: Duration of pregnancy and puerperium ] [ Designated as safety issue: Yes ]
  • Preeclampsia [ Time Frame: Pregnancy > 20 weeks gestation ] [ Designated as safety issue: Yes ]
  • IUFD [ Time Frame: Pregnancy >24 weeks gestation ] [ Designated as safety issue: No ]
  • Preterm Delivery [ Time Frame: 24 weeks gestation<Pregnancy <37weeks gestation ] [ Designated as safety issue: No ]
  • Spontaneous Osteoporotic Fractures [ Time Frame: Duration of pregnancy and puerperium ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Low-molecular-weight Heparin (LMWH) Versus Unfractionated Heparin (UFH) in Pregnant Women With Recurrent Abortion Secondary to Antiphospholipid Syndrome
Low-molecular-weight Heparin Versus Unfractionated Heparin in Pregnant Women With History of Recurrent Abortion Secondary to Antiphospholipid Syndrome. A Randomized Controlled Trial

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).

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Abortion
  • 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.
    Other Name: Clexane 40 mg
  • 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 .
    Other Name: Cal-Heparine
  • Experimental: enoxaparin 40 mg plus low dose aspirin
    Intervention: Drug: enoxaparin 40mg plus low dose aspirin
  • Active Comparator: Heparin calcium 5,000 U twice daily plus low dose aspirin
    Intervention: Drug: Heparin calcium5,000 U twice daily plus low dose aspirin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
60
December 2009
November 2009   (final data collection date for primary outcome measure)

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.
Female
19 Years to 37 Years
No
Contact information is only displayed when the study is recruiting subjects
Egypt
 
NCT01051778
Aps/UFH/enox40
Yes
Usama M. Fouda, Ahmed M .Sayed, Cairo university
Cairo University
Ahmed Elgazzar Hospital
Principal Investigator: Usama M Fouda Lecturer of obstetrics and Gynecology , Cairo university
Principal Investigator: Ahmed M Sayed Assistant professor of obstetrics and Gynecology , Cairo university.
Cairo University
January 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP