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Completed

NCT Number: NCT02672566

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

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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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

Chru Brest, Brest, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Enoxaparin

Drug

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

Other names: Treatment

Usual Care

Other

Patients will all benefit from the usual care

Other names: Classic support

Primary outcomes

  1. Number of new born with a weight inferior at the 10th percentile

    Time frame: Week 36

    With the AUDIPOG formula, the number of new born with a weight inferior at the 10th percentile will be calculated.

Secondary outcomes

  1. Change in doppler parameters of uterine arterie

    Time frame: baseline from delivery

    Doppler parameters is a composite outcome : pulsatility index and presence of notch

  2. Change in doppler parameters of ombilical arterie

    Time frame: baseline from delivery

    Doppler parameters is a composite outcome : resistance index, presence of a zero diastole or reverse flow

  3. Change in doppler fetal weight

    Time frame: baseline from delivery

    doppler fetal weight (grams)

  4. birth weight

    Time frame: delivery

    birth weight (grams)

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

    Time frame: delivery

    With the AUDIPOG formula, the number of new born with a weight inferior at the 3rd percentile will be calculated.

  6. Number of fetal extraction

    Time frame: before 36 weeks of gestation

    fetal extraction

  7. number of major neonatal parameters

    Time frame: 1 month after delivery

    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

  8. number of minor neonatal parameters

    Time frame: 1 month after delivery

    Minor neonatal parameters is a composite outcome : Caesarean section for fetal distress, Cord arterial pH < 7.1, Apgar score <7 at 5 minutes

  9. Number of Major bleeding events (MB) and clinically relevant non-major bleeding events (CRNMB)

    Time frame: from randomisation to 1 month postpartum

    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.

  10. Number of thrombocytopenia

    Time frame: From randomisation to 36 weeks

    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

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Saint Etienne

Other

Registry information

Official study title

Low-molecular-weight Heparin in Constituted Vascular Intrauterine Growth Restriction. Randomized Multicenter Trial

Acronym: GROWTH

Important dates

Study start
2016
Primary completion
2019
Study completion
2020
First posted
Feb 3, 2016
Registry last updated
Mar 20, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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