Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction (GROWTH)

Centre Hospitalier Universitaire de Saint Etienne

Status and phase: Completed; Phase 3

Conditions: Fetal Growth Retardation

Treatments: Other: Usual care; Drug: Enoxaparin

Study type: Interventional

Funder types: Other

Identifiers

NCT02672566

2016-000424-25 (EudraCT Number)

1508175

Details and patient eligibility

About

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.

Enrollment: 82 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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82 participants in 2 patient groups

Experimental group : enoxaparin

Experimental group

Description:

Experimental group will take enoxaparin (4000 Ui / Day) and will benefit from the usual care.

Treatment:

Drug: Enoxaparin

Other: Usual care

Control group

Active Comparator group

Description:

The control group will only benefit from the usual care.

Treatment:

Other: Usual care