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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-000424-25 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental group : enoxaparin | Experimental | Experimental group will take enoxaparin (4000 Ui / Day) and will benefit from the usual care. |
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| Control group | Active Comparator | The control group will only benefit from the usual care. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin | Drug | Enoxaparin will be delivered to the patients every day at the dose of 4 000 Ui. |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of new born with a weight inferior at the 10th percentile | With the AUDIPOG formula, the number of new born with a weight inferior at the 10th percentile will be calculated. | Week 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in doppler parameters of uterine arterie | Doppler parameters is a composite outcome : pulsatility index and presence of notch | baseline from delivery |
| Change in doppler parameters of ombilical arterie |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tiphaine Raia-Barjat, MD | Centre Hospitalier Universitaire de Saint Etienne | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chru Brest | Brest | France | ||||
| Chu Clermont-Ferrand |
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| ID | Term |
|---|---|
| D005317 | Fetal Growth Retardation |
| ID | Term |
|---|---|
| D005315 | Fetal Diseases |
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D017984 | Enoxaparin |
| D013812 | Therapeutics |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
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| Usual care | Other | Patients will all benefit from the usual care |
|
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Doppler parameters is a composite outcome : resistance index, presence of a zero diastole or reverse flow
| baseline from delivery |
| Change in doppler fetal weight | doppler fetal weight (grams) | baseline from delivery |
| birth weight | birth weight (grams) | delivery |
| Number of new born with a weight inferior at the 3rd percentile | With the AUDIPOG formula, the number of new born with a weight inferior at the 3rd percentile will be calculated. | delivery |
| Number of fetal extraction | fetal extraction | before 36 weeks of gestation |
| number of major neonatal parameters | Major neonatal parameters is at least one or more : Perinatal death, Ischemic encephalopathy Major intra- or periventricular bleeding (grade 3 or 4), Periventricular leukomalacia, Necrotizing enterocolitis, Bronchopulmonary dysplasia or Sepsis | 1 month after delivery |
| number of minor neonatal parameters | Minor neonatal parameters is a composite outcome : Caesarean section for fetal distress, Cord arterial pH < 7.1, Apgar score <7 at 5 minutes | 1 month after delivery |
| Number of Major bleeding events (MB) and clinically relevant non-major bleeding events (CRNMB) | The definitions of major bleeding events and clinically major bleeding events are adapted from the ISTH definition for which were added a specific Obstetrics and Gynaecology definition Bleeding events (MB) is a composite outcome. | from randomisation to 1 month postpartum |
| Number of thrombocytopenia | thrombocytopenia is a composite outcome : Thrombopenia defined by platelet count < 100 G/L Significant thrombocytopenia with HIT suspicion defined as follows:≥ 40% decline of the platelet count (compared with baseline value) occurring during the first 8 weeks following the start of HBPM Or platelet count < 80 Giga/l to terme | From randomisation to 36 weeks |
| Clermont-Ferrand |
| 63003 |
| France |
| Chu Grenoble | Grenoble | 38000 | France |
| Ch Lyon Sud Pierre Benite | Lyon | France |
| HFME - Lyon Est | Lyon | France |
| Hopital Croix Rousse Lyon | Lyon | France |
| Ch Roanne | Roanne | France |
| Chu Saint Etienne | Saint-Etienne | 42100 | France |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006130 | Growth Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D002241 |
| Carbohydrates |