Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction. Randomized Multicenter Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 82
- 试验地点
- 8
- 主要终点
- Number of new born with a weight inferior at the 10th percentile
研究概览
简要总结
Intrauterine growth restriction (IUGR) is correlated to an abnormal placenta development, with an alteration of the maternal-fetal circulation, coagulation troubles, and apparition of placental infarcts. IUGR represents the third cause of perinatal mortality in France, and is associated to an important morbidity. For birth-weights < 10th percentile of the gestational age, the neonatal death risk is doubled, compared to abnormal weights. In 35% of cases, IUGR is of vascular origin and is included in the broader framework of placental vascular pathology (PVP).
Up to now, studies have focused on the primary or secondary prevention of PVP. Few studies have evaluated the treatment of constituted vascular IUGR. Currently, the management of vascular IUGR is mainly based on active surveillance, or termination of pregnancy. Pathological findings suggest that placental pro-thrombotic phenomena play a role in the constitution of vascular IUGR. Since aspirin is not effective in reducing this type of event, a randomized, open-label study conducted in China compared 14-day treatment with low-molecular-weight heparin (LMWH) versus Dan-Shen (a product not used in France) after diagnosis of IUGR. This trial, including 73 patients, showed a significant improvement in average growth kinetics in the LMWH group. The mean birth weight was 2877 g in the heparin group and 2492 g in the Dan-Shen group (p <0.0001). However, no data were provided concerning the number of newborns with a birth weight <10th percentile, i.e. the risk of morbidity and mortality, or complications occurring. Due to the lack of reliable data, LMWH are not included in the currently recommended therapeutic strategy for vascular IUGR.
The studies in IUGR reported to date mainly focused on primary or secondary prevention in women at risk of PVP, assessing the value of aspirin, which showed only a modest effect. No effective therapeutic strategy is available to treat patients with constituted vascular IUGR, a situation where LMWH should be more effective than antiplatelets given the vascular context.
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
- •Patient over 18 years being at a gestational age ≥ 22 and <34 weeks of gestation with vascular fetal growth retardation defined according CNGOF
- •Ultrasound Estimated fetal weight below the 10th percentile
- •Clinical and ultrasound findings suggesting pathologically impaired growth or diminished foetal well-being
- •Clinical and ultrasound findings suggesting placental insufficiency
- •Precise dating of pregnancy with an ultrasound between 11 + 0 and 13 + 6 weeks of gestation
- •Written informed consent
排除标准
- •multiple pregnancy or identified cause of IUGR (intra-uterine growth retardation)
- •Patient with an immediate indication of fetal extraction
- •Women with a history of venous thromboembolism or already treated with anti-coagulant
- •Women with a contraindication to enoxaparin treatment at prophylactic doses
- •Patient refusing to participate or unable to consent
- •Patient with less than 80,000 platelets / mm 3 with the initial assessment
研究组 & 干预措施
Experimental group : enoxaparin
Experimental group will take enoxaparin (4000 Ui / Day) and will benefit from the usual care.
干预措施: Enoxaparin (Drug)
Experimental group : enoxaparin
Experimental group will take enoxaparin (4000 Ui / Day) and will benefit from the usual care.
干预措施: Usual care (Other)
Control group
The control group will only benefit from the usual care.
干预措施: Usual care (Other)
结局指标
主要结局
Number of new born with a weight inferior at the 10th percentile
时间窗: Week 36
With the AUDIPOG formula, the number of new born with a weight inferior at the 10th percentile will be calculated.
次要结局
- birth weight(delivery)
- number of major neonatal parameters(1 month after delivery)
- Change in doppler parameters of uterine arterie(baseline from delivery)
- Change in doppler fetal weight(baseline from delivery)
- number of minor neonatal parameters(1 month after delivery)
- Change in doppler parameters of ombilical arterie(baseline from delivery)
- Number of new born with a weight inferior at the 3rd percentile(delivery)
- Number of fetal extraction(before 36 weeks of gestation)
- Number of Major bleeding events (MB) and clinically relevant non-major bleeding events (CRNMB)(from randomisation to 1 month postpartum)
- Number of thrombocytopenia(From randomisation to 36 weeks)