Role of LMWH (Enoxaparine) With or Without Aspirin in the Prevention of Habitual Abortion; Special Attention to the Thrombophilic Status of the Mother
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Pregnancy outcome: livebirths (>37 weeks of gestation), premature livebirths (> 24, but <37 weeks of gestation)
研究概览
简要总结
1 % of all pregnancies end in habitual/recurrent abortion. In about half of women with habitual abortions (HAB) hereditary or acquired (antiphospholipid antibodies) thrombophilia are observed. The investigators wanted to test whether antithrombotic treatment (Low-Molecular Weight Heparin, LMWH, ASA or both combined)would prevent these women from a subsequent abortion. Depending on thrombophilic status the women included in one of the three sub-studies: HABENOX 1 (mild, single thrombophilia), HABENOX 2 (no known thrombophilia), HABENOX 3 (moderate to severe thrombophilia, with combined thrombophilia or moderate to high titer antiphospholipid antibodies).
Study design: Randomised placebo controlled multicenter study.
Number of patients per study: 90 patients per group, 270 altogether.
Timetable: Starting 2/2002, finishing 31.12.2007.
Time frame: >37 weeks of gestation and >24, but <37 weeks of gestation (premature)
Treatment started before 7. gw.
HABENOX 1 and 2:
Study groups:
Group 1 : Enoxaparin 40 mg+ placebo, Group 2: Enoxaparin 40 +ASA 100 mg, Group 3: ASA.
HABENOX 3:
Study groups:
Group 1: Enoxaparin 40 twice daily+ placebo o.d., Group 2: Enoxaparin 40 mg twice daily +ASA 100 mg o.d.
Primary end-points:
Pregnancy outcome: livebirths ( ≥37 weeks of gestation), premature livebirths (≥24, but <37 weeks of gestation)
Secondary end-points: Bleeding complications, intrauterine growth retardation (<-2SD), pre-eclampsia, abruptio placentae,
Ending: In the group of combined medication, tablets will be stopped at 36 weeks of gesta-tion. LMWH will be started in all patients after delivery and continued 6 weeks postpartum.
详细描述
Background: The prevalence of spontaneous abortions is 1000-1500/10000 pregnancies per year meaning that 10-15% of all pregnancies will end in an abortion; 1/10 of these abortions are recurrent (1 % of all pregnancies). In about half of women with habitual abortions (HAB) hereditary (F V Leiden, F II (prothrombin) mutation, Protein C, S deficiency and anti-thrombin) or acquired (antiphospholipid antibodies) thrombophilia are observed. Efficacy of the medical treatment of patients with a history of HAB has yet to be completely demonstrated. We have recently shown that low-molecular-weight heparin (LMWH) is as effective as unfractionated heparin in prevention of thromboembolic complications in pregnant women and causes less bleeding complications (UFH) and has no osteoporotic effect. LMWH could be safer than UF-heparin during long treatment periods (7-8 months).
Study design: Randomised placebo controlled multicenter study.
Centers: Helsinki (2), Oulu (1), Stockholm (1), Leiden (1)
Number of patients per study: 90 patients per group, 270 altogether
Timetable: Starting 2/2002, finishing 31.12.2007
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Habenox 1: Three or more consecutive abortions of first trimester (ad h 12+6 wks) or two second trimester abortions (ad h 13 wks-23+6 wks) or one third trimester abortion (24 weeks or more) with one first-second trimester abortions and one thrombophiliatest positive: F V Leiden (heterozygote) or protein C or S deficiency, or anticardiolipin antibodies (low to moderate level), prothrombin gene mutation, or high level of F VIII.
- •HABENOX 2: The thrombophilic tests above are negative.
- •HABENOX 3:positive combined thrombophilia, F V Leiden (homozygote), anticardiolipin antibodies (high level >40) , lupusanticoagulant, or AT III deficiency.
排除标准
- •History of DVT or pulmonary embolism.
- •Significant bleeding history.
研究组 & 干预措施
ASA
The patients received either Enoxaparine+placebo, Enoxaparine+ASA (Aspirin 100 mg) or ASA alone.ASA or placebo were blinded in the two first groups.
干预措施: Aspirin (Drug)
Klexane
Clexane (enoxaparine) 40 mg sc
干预措施: Klexane (Drug)
Aspirin and Enoxaparine
干预措施: Klexane and ASA (Drug)
结局指标
主要结局
Pregnancy outcome: livebirths (>37 weeks of gestation), premature livebirths (> 24, but <37 weeks of gestation)
时间窗: gestational weeks >37 and gestational weeks > 24, but <37
次要结局
- Bleeding complications, intrauterine growth retardation (<-2SD), pre-eclampsia, abruption placenta(gestational weeks > 37 and gestational weeks >24, but <37)