Thrombophilia in Pregnancy Prophylaxis Study: a multicentre, multinational, randomised controlled trial of prophylactic low molecular weight heparin in high-risk pregnant thrombophilic women.

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