TIPPS - Thrombophilia in Pregnancy Prophylaxis Study: A Multicentre, Multinational, Randomized Control Trial of Prophylaxis Low Molecular Weight Heparin (LMWH) in High-risk Thrombophilic Women.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 292
- 试验地点
- 12
- 主要终点
- The primary objective of the 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 fetal loss)
研究概览
简要总结
The TIPPS trial seeks to determine the safety and effectiveness of low-molecular-weight heparin (LMWH), an anticoagulant, in preventing placenta mediated pregnancy complications and venous thromboembolism (VTE) in women with thrombophilia. Thus, the principal research question is: can LMWH prevent thrombosis in the leg veins, pulmonary arteries and placental vessels, thereby reducing the risk of deep vein thrombosis, pulmonary embolism (PE), intrauterine growth restriction (IUGR), preeclampsia, miscarriage and stillbirth?
详细描述
TIPPS is a multicentre, multi-national open-label randomized controlled clinical trial. Two hundred and eighty-four thrombophilic women at risk for VTE or placenta mediated pregnancy complications will be recruited. Patients who require anticoagulant prophylaxis during this pregnancy (as judged by the local investigator) or have participated in TIPPS before will not be eligible for the trial.
The study consists of five periods: screening, randomization, antenatal follow-up, labour and delivery, and the post-partum follow-up.
Eligible and consenting patients will be assigned to one of two groups (treatment or control), stratified by gestational age at randomization: less than 8 weeks, 8 weeks +1 day to 12 weeks , 12 weeks +1 day to 19 weeks + 6 days.
Treatment Group - Subjects randomized to the treatment group will receive daily injections of dalteparin during the ante-natal period. They will be taught how to self-administer sub-cutaneous injections of dalteparin 5000 International units (IU) once daily (o.d.) until gestational week 20, then twice daily (bid) until 37 weeks gestation or onset of labour.
Control Group- Subjects randomized to control will receive identical obstetrical care and follow-up, but no ante-natal dalteparin.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •One or more of the following:
- •Previous preeclampsia
- •Previous unexplained intra-uterine growth restriction
- •Previous recurrent miscarriage:
- •three(3) or more unexplained miscarriage at less than 10 weeks gestation;
- •two (2) or more unexplained fetal loss between 10 and 16 weeks gestation;
- •one (1) or more unexplained fetal loss at or greater than 16 weeks gestation
- •Previous abruptio placenta
- •Previous personal history of VTE:
- •Previous documented secondary proximal VTE,
- •Previous documented calf-vein thrombosis (idiopathic or secondary),
- •Previous superficial phlebitis
- •First degree relative with symptomatic thrombophilia
- •Pregnancy - > 4weeks gestation and < 20 weeks gestation
- •Thrombophilia:
- •Two abnormal tests, and no normal tests
- •3.1 Protein S
- •3.2 Protein C
- •3.3 Antithrombin
- •Two positive tests
- •3.4 Anticardiolipin immunoglobulin M (IgM) (>30 U/ml)
- •3.5 Anticardiolipin immunoglobulin G (IgG) (>30 U/ml)
- •3.6 Anti-b2 glycoprotein IgG (>20 U/ml)
- •3.7 Anti-b2 glycoprotein IgM (>20 U/ml)
- •3.8 Lupus anticoagulant
- •One positive test
- •3.9 Factor V Leiden (heterozygous or homozygous)
- •3.10Prothrombin gene defect (heterozygous or homozygous)
排除标准
- •Less than 4 weeks gestation or greater than 20 weeks gestation
- •No confirmed thrombophilia
- •Contraindication to heparin therapy
- •History of heparin induced thrombocytopenia
- •Platelet count less than 100,000 109/L
- •History of osteoporosis or steroid use
- •Actively bleeding
- •Documented peptic ulcer within 6 weeks
- •Heparin, bisulfite or fish allergy
- •Severe hypertension (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >120mmHg)
- •Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
- •Severe hepatic failure (INR >1.8)
- •Geographic inaccessibility
- •Need for anticoagulants, discretion of the investigator such as but not limited to:
- •Recurrent fetal loss and phospholipid antibody syndrome
- •Prior idiopathic proximal VTE:
- •History of idiopathic deep venous thrombosis (DVT) or pulmonary embolism (PE) treated with anticoagulants (> 1 month of heparin or warfarin) or inferior vena cava (IVC) interruption;
- •Idiopathic is a VTE occurring outside all of the following periods: antepartum, postpartum, oral contraceptive use, surgery, immobilization, cast, and malignancy
- •Mechanical heart valve
- •Legal lower age limitations (country specific)
- •Prior participation in TIPPS
- •Unable/unwilling to provide informed consent
研究组 & 干预措施
dalteparin sodium
Subjects randomized to the treatment group will receive daily injections of dalteparin during the antenatal period. They will be taught how to self-administer sub-cutaneous injections of dalteparin 5000 IU once daily (o.d.) until gestational age 20, then twice daily (bid) until 37 weeks gestation or onset of labour.
Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum
干预措施: dalteparin sodium (Drug)
结局指标
主要结局
The primary objective of the 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 fetal loss)
时间窗: 6 weeks post-partum
次要结局
- Determine the safety of LMWH use in pregnancy (Specifically rates of bleeding, thrombocytopenia and fractures)(6 weeks post-partum)
- Identify if prophylactic LMWH will reduce rates of pregnancy induced hypertension (PIH), preterm labor and abruptio placenta in pregnant thrombophilic women compared to control(6 weeks post-partum)
- Identify whether prolonged use of LMWH in pregnancy results in decreased bone mineral density (BMD) compared to control(6 weeks post-partum)