Phase III Study Analyzing the Effectiveness of Dalteparin Therapy as Intervention in Recurrent Pregnancy Loss
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 449
- 试验地点
- 12
- 主要终点
- ongoing intact pregnancy at 24 weeks of gestation
研究概览
简要总结
With this clinical trial the investigators will analyze whether the rate of pregnancy losses before the 24th week of gestation can be reduced by dalteparin treatment in habitual aborters.
详细描述
Recurrent pregnancy loss (RPL) is a common health problem with three or more loses affecting 1-2% and two or more losses affecting up to 5% of women at the reproductive age (Brenner 2003).
Several aetiologies have been identified or are under discussion to play a role in RPL, including chromosomal translocations and inversions, anatomic alterations of the uterus, endocrinological abnormalities, autoimmune disorders infection, smoking and alcohol consumption, exposure to environmental factors as well as coagulation and immunoregulatory defects (Pandey 2005, Lee 2000). About 30-40% of cases of RPL remain unexplained after standard gynaecological, hormonal and karyotype analysis (Rey 2000).
As stated by Pandey et al (Pandey 2005), a successful implantation during pregnancy requires a balanced equilibrium between coagulation, fibrinolysis and vascular remodeling by the process of angiogenesis in order to avoid excess fibrin accumulation in placental vessels and intervillous spaces (Buchholz 2003). However, thrombosis in decidual vessels is reported to be one of the major causes of RPL (Arias 1998) and could be explained by excessive thrombosis of the placental vessels, placental infarction, and secondary uteroplacental insufficiency.
Recurrent pregnancy loss is a well-described complication of the antiphospholipid antibody syndrome and is thought to be associated with thrombosis of placental vessels, often with evidence for placental infarction. More recently, inherited thrombophilic abnormalities have been linked to RPL and other obstetric complications. At least 16 case-control studies found a high prevalence of factor V Leiden (FVL) in women with unexplained RPL (up to 30%) compared to 1% to 10% of control subjects with odds ratios ranging from 2 to 5 (Press et al. 2002). Likewise, other thrombophilic risk factors including factor II G20210A, hyperhomocysteinemia, protein C, protein S and antithrombin deficiencies have also been associated with RPL (Sanson 1996; Brenner 1999).
A meta-analysis of Rey et al. (Rey 2003) including 31 case control, cohort and cross-sectional studies, showed an association between thrombophilia and fetal loss, though the magnitude varies according to type of fetal loss and type of thrombophilia.
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
- •Single pregnancy, 5th to 8th week of gestation
- •Documented foetal heart activity in US
- •History of recurrent pregnancy loss, defined as:
- •2 or more early (< 12 weeks of gestation) pregnancy losses or
- •1 or more late (> 12 weeks of gestation) pregnancy loss
- •at least 18 years of age
- •Written informed consent of the patient
排除标准
- •Previous pregnancy losses caused by foetal structural or chromosomal anomalies
- •Uterine anomalies
- •Maternal infection which caused previous pregnancy loss
- •Risk group II or III according to ETHIG I risk stratification (clinical need for heparin prophylaxis)
- •Acute thromboembolic event (need of heparin therapy)
- •Known hypersensitivity to any of the trial drugs or its ingredients (i.e. thrombocytopenia type II caused by allergic reaction to heparin)
- •Antiphospholipid antibody syndrome
- •Diabetes mellitus
- •Ongoing nicotine or drug or alcohol abuse
- •Known HIV infection
- •Expected low compliance (e.g. by travel distance to trial site)
- •Current or recent (within 30 days prior to start of trial treatment) treatment with another investigational drug or participation in another investigational trial
研究组 & 干预措施
Multivitamin supplement
干预措施: Multivitamin supplement (Dietary Supplement)
Multivitamin supplement + dalteparin sodium
干预措施: Fragmin P Forte (dalteparin sodium) (Drug)
结局指标
主要结局
ongoing intact pregnancy at 24 weeks of gestation
时间窗: at 24 weeks of gestation
次要结局
- preterm delivery (< 37 weeks of gestation)(6-8 weeks after delivery)
- foetus with structural anomalies(6-8 weeks after delivery)
- side effects of dalteparin therapy (e.g. thrombocytopenia, osteoporosis, haemorrhage)(6-8 weeks after delivery)
- life birth(6-8 weeks after delivery)
- late pregnancy complication, defined as at least one of the following: preterm delivery, placenta insufficiency, intrauterine growth retardation, preeclampsia and abruptio placentae(6-8 weeks after delivery)
研究者
Ekkehard Schleussner
Sponsor-Investigator
University of Jena