None listed
Conditions
Brief summary
Study rationale: Thrombophilias are disorders that result in a predisposition to develop Venous Thromboembolic Events (VTEs). Thrombophilias are common in the general population. Recent evidence indicates that women with thrombophilia not only have an increased risk of VTEs during pregnancy, but also increased risk of pre-eclampsia, intrauterine growth restriction (IUGR), abruptio placentae and foetal loss. The management of thrombophilic women in pregnancy is controversial and antithrombotic prophylaxis may reduce the rate of complications in pregnancy and the rate of VTEs. Phase II studies with low molecular weight heparin (LMWH) in pregnant women, for a variety of indications, suggest that there may be a benefit to their use in this high-risk group. However, to date there have been no controlled clinical trials using LMWH to prevent pre-eclampsia, IUGR or foetal loss. The purpose of this study is to determine the safety and efficacy of LMWH in preventing VTE, pre-eclampsia, IUGR and foetal loss in pregnant thrombophilic women. Study design: This study is a multi-centre, open-label, randomised controlled clinical trial based in a maximum of 30 centres. Three hundred and eighty-five(385) pregnant women with confirmed thrombophilia and at high risk for pregnancy complications will be randomised to prophylactic dose dalteparin or control (identical follow-up and care, but no drug intervention). The study will consist of five periods: a screening period, randomisation, antenatal follow-up, labour and delivery, and postpartum follow-up. Maximum time on study will vary between 26 and 46 weeks. The primary objective of this study is to identify if LMWH prophylaxis in thrombophilic pregnant women results in a greater than 33% relative risk reduction in the composite outcome measure (VTE, pre-eclampsia, IUGR and foetal loss) compared to control. Secondary objectives will be to: 1. Identify if prophylactic LMWH will reduce rates of PIH, pre-term labour and abruptio placentae in pregnant thrombophilic women compared to control. 2. Determine safety of LMWH use in pregnancy (specifically rates of bleeding, thrombocytopenia and fractures). 3. Identify whether prolonged LMWH use in pregnancy results in decreased BMD compared to control
Interventions
Dalteparin sodium 5000U given subcutaneously (s.c., under the skin) once daily up to 20 weeks gestation, then 5000U s.c. twice daily from 20 weeks gestation to 37 weeks gestation or delivery. All participants will receive Fragmin 5000U s.c. daily from post-partum day 1 for 6 weeks.
Sponsors
The Ottawa Health Research Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
High-risk pregnant women with a confirmed thrombophilia, who have had any of the following pregnancy complications: recurrent miscarriages, stillbirth, pre-eclampsia, very small birth weight baby (IUGR), bleeding in the placenta before delivery (called abruptio placentae) or previous VTE or first degree relative with a history of VTE and confirmed thrombophilia. To be eligible women must give informed consent and be over 18 years of age.
Exclusion criteria
Less than 4 weeks or greater than 20 weeks pregnant. No confirmed thrombophilia. Unwilling or unable to give informed consent. Contraindication to heparin therapy, including: previous heparin induced thrombocytopenia, platelet count of less than 100,000x10^6/L, history of osteoporosis or steroid use, actively bleeding, documented peptic ulcer. Sensitivity or allergy to pork products. Severe hypertension, severe liver or kidney failure. Need for anticoagulation - i.e. women with recurrent fetal loss and known Anti-Phospholipid Antibody Syndrome, women with prior history of idiopathic VTE and mechanical heart valves.
Outcome results
None listed