Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction

NCT ID: NCT02672566

Last Updated: 2020-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-22
• Study Completion Date: 2020-01-22

Brief Summary

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.

Conditions

Fetal Growth Retardation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental group : enoxaparin

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

Group Type: EXPERIMENTAL

Enoxaparin

Intervention Type: DRUG

Enoxaparin will be delivered to the patients every day at the dose of 4 000 Ui.

Usual care

Intervention Type: OTHER

Patients will all benefit from the usual care

Control group

The control group will only benefit from the usual care.

Group Type: ACTIVE_COMPARATOR

Usual care

Intervention Type: OTHER

Patients will all benefit from the usual care

Interventions

Enoxaparin

Enoxaparin will be delivered to the patients every day at the dose of 4 000 Ui.

Intervention Type: DRUG

Usual care

Patients will all benefit from the usual care

Intervention Type: OTHER

Other Intervention Names

Treatment; Classic support

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tiphaine Raia-Barjat, MD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

Chru Brest

Brest, , France

Chu Clermont-Ferrand

Clermont-Ferrand, , France

Chu Grenoble

Grenoble, , 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, , France

Countries

France

Other Identifiers

2016-000424-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1508175

Identifier Type: -

Identifier Source: org_study_id