Recurrent Abortion
Conditions
Keywords
Recurrent abortion, Antiphospholipid syndrome, unfractionated heparin, Low Molecular Weight Heparin
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).
Interventions
DRUGenoxaparin 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.
DRUGHeparin 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 .
Sponsors
Ahmed Elgazzar Hospital
Cairo University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
19 Years to 37 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live Birth Rate = (Number of Live Births / Total Number of Pregnancies) | pregnancy > 24weeks gestation | 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
| Measure | Time frame |
|---|---|
| Thrombocytopenia | Duration of pregnancy and puerperium |
| Preeclampsia | Pregnancy > 20 weeks gestation |
| Minor and Major Bleeding | Duration of pregnancy and puerperium |
| Preterm Delivery | 24 weeks gestation<Pregnancy <37weeks gestation |
| Spontaneous Osteoporotic Fractures | Duration of pregnancy and puerperium |
| IUFD | Pregnancy >24 weeks gestation |
Countries
Egypt
Participant flow
Recruitment details
This study was conducted between June 2006 to December 2009 at Cairo university hospital and Ahmed Elgazzar hospital ,Cairo.
Participants by arm
| Arm | Count |
|---|---|
| Enoxaparin 40 mg /Day Plus Low Dose Aspirin | 30 |
| Heparin Calcium 5,000 U Twice Daily Plus Low Dose Aspirin | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Heparin Calcium 5,000 U Twice Daily Plus Low Dose Aspirin | Enoxaparin 40 mg /Day Plus Low Dose Aspirin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 30 Participants | 60 Participants |
| Age Continuous | 28.57 years STANDARD_DEVIATION 3.48 | 27.47 years STANDARD_DEVIATION 3.2 | 28.016 years STANDARD_DEVIATION 3.362 |
| Region of Enrollment Egypt | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
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.
Time frame: pregnancy > 24weeks gestation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enoxaparin 40 mg /Day Plus Low Dose Aspirin | Live Birth Rate = (Number of Live Births / Total Number of Pregnancies) | 24 Percentage of pregnancies |
| Heparin Calcium 5,000 U Twice Daily Plus Low Dose Aspirin | Live Birth Rate = (Number of Live Births / Total Number of Pregnancies) | 20 Percentage of pregnancies |
Secondary
IUFD
Time frame: Pregnancy >24 weeks gestation
Secondary
Minor and Major Bleeding
Time frame: Duration of pregnancy and puerperium
Secondary
Preeclampsia
Time frame: Pregnancy > 20 weeks gestation
Secondary
Preterm Delivery
Time frame: 24 weeks gestation<Pregnancy <37weeks gestation
Secondary
Spontaneous Osteoporotic Fractures
Time frame: Duration of pregnancy and puerperium
Secondary
Thrombocytopenia
Time frame: Duration of pregnancy and puerperium