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

NCT02672566 | Completed Phase 3 DMC

• 2 other identifiers: 15081752016-000424-25
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 8

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

Keywords

Fetal Growth Retardation; enoxaparin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• Change in doppler parameters of uterine arterie

  baseline from delivery

• Change in doppler parameters of ombilical arterie

  baseline from delivery

• Change in doppler fetal weight

  baseline from delivery

• birth weight

  delivery

• Number of new born with a weight inferior at the 3rd percentile

  delivery

Study Arms (2)

Experimental group : enoxaparin

EXPERIMENTAL

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

Drug: Enoxaparin; Other: Usual care

Control group

ACTIVE COMPARATOR

The control group will only benefit from the usual care.

Other: Usual care

Interventions

Enoxaparin DRUG

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

Also known as: Treatment

Experimental group : enoxaparin

Usual care OTHER

Patients will all benefit from the usual care

Also known as: Classic support

Control group; Experimental group : enoxaparin

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead

Study Sites (8)

Chru Brest

Brest, France

Location

Chu Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Chu Grenoble

Grenoble, 38000, France

Location

Ch Lyon Sud Pierre Benite

Lyon, France

Location

HFME - Lyon Est

Lyon, France

Location

Hopital Croix Rousse Lyon

Lyon, France

Location

Ch Roanne

Roanne, France

Location

Chu Saint Etienne

Saint-Etienne, 42100, France

Location

MeSH Terms

Conditions

Fetal Growth Retardation

Interventions

Enoxaparin; Therapeutics

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Tiphaine Raia-Barjat, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 3, 2016
• Study Start: July 22, 2016
• Primary Completion: September 5, 2019
• Study Completion: January 22, 2020
• Last Updated: March 20, 2020

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)