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
  Purpose

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).


Condition Intervention Phase
Recurrent Abortion
Drug: enoxaparin 40mg plus low dose aspirin
Drug: Heparin calcium5,000 U twice daily plus low dose aspirin
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Cairo University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 60
Study Start Date: June 2006
Study Completion Date: December 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: enoxaparin 40 mg plus low dose aspirin 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
Active Comparator: Heparin calcium 5,000 U twice daily plus low dose aspirin 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

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).

  Eligibility

Ages Eligible for Study:   19 Years to 37 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01051778

Locations
Egypt
Ahmed Elgazzar hospital
Cairo, Egypt
Cairo university hospital
Cairo, Egypt
Sponsors and Collaborators
Cairo University
Ahmed Elgazzar Hospital
Investigators
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.
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Usama M. Fouda, Ahmed M .Sayed, Cairo university
ClinicalTrials.gov Identifier: NCT01051778     History of Changes
Other Study ID Numbers: Aps/UFH/enox40
Study First Received: January 19, 2010
Results First Received: May 10, 2010
Last Updated: July 29, 2011
Health Authority: Egypt: Institutional Review Board

Keywords provided by Cairo University:
Recurrent abortion
Antiphospholipid syndrome
unfractionated heparin
Low Molecular Weight Heparin

Additional relevant MeSH terms:
Antiphospholipid Syndrome
Abortion, Habitual
Abortion, Spontaneous
Pregnancy Complications
Autoimmune Diseases
Immune System Diseases
Aspirin
Heparin
Calcium heparin
Heparin, Low-Molecular-Weight
Dalteparin
Enoxaparin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014