Clinical trial NCT02672566: Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction
Official title: Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction. Randomized Multicenter Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fetal Growth Retardation
Keywords: Fetal Growth Retardation
enoxaparin
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2016-02-03
Enrollment: 82
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of new born with a weight inferior at the 10th percentile
timeFrame: Week 36
Secondary outcomes:
measure: Change in doppler parameters of uterine arterie
timeFrame: baseline from delivery
measure: Change in doppler parameters of ombilical arterie
timeFrame: baseline from delivery
measure: Change in doppler fetal weight
timeFrame: baseline from delivery
measure: birth weight
timeFrame: delivery
measure: Number of new born with a weight inferior at the 3rd percentile
timeFrame: delivery
measure: Number of fetal extraction
timeFrame: before 36 weeks of gestation
measure: number of major neonatal parameters
timeFrame: 1 month after delivery
measure: number of minor neonatal parameters
timeFrame: 1 month after delivery
measure: Number of Major bleeding events (MB) and clinically relevant non-major bleeding events (CRNMB)
timeFrame: from randomisation to 1 month postpartum
measure: Number of thrombocytopenia
timeFrame: From randomisation to 36 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: Chru Brest
city: Clermont Ferrand
country: France
facility: Chu Clermont-Ferrand
city: Grenoble
country: France
facility: Chu Grenoble
city: Lyon
country: France
facility: Ch Lyon Sud Pierre Benite
city: Lyon
country: France
facility: HFME - Lyon Est
city: Lyon
country: France
facility: Hopital Croix Rousse Lyon
city: Roanne
country: France
facility: Ch Roanne
city: St Etienne
country: France
facility: Chu Saint Etienne
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Tiphaine Raia-Barjat, MD
role: PRINCIPAL_INVESTIGATOR
References: