Treatment of Intrauterine Growth Restriction With Low Molecular Heparin.

Study Overview
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Brief Summary
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TREATMENT OF INTRAUTERINE GROWTH RESTRICTION WITH LOW MOLECULAR WEIGHT HEPARIN.

Detailed Description
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TREATMENT OF INTRAUTERINE GROWTH RESTRICTION WITH LOW MOLECULAR WEIGHT HEPARIN: RANDOMIZED CLINICAL TRIAL (TRACIP STUDY).

Official Title
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Treatment of Intrauterine Growth Restriction With Low Molecular Heparin: Randomized Clinical Trial. Tratamiento Del Crecimiento Intrauterino Restringido Precoz Con Heparina de Bajo Peso Molecular: Ensayo clínico Aleatorizado.

Conditions
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Intrauterine Growth Restriction

Intervention / Treatment
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* Drug: Low molecular weight heparin
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women older than 18 years. Unique gestations Diagnosis of early placental intrauterine growth (according to Delphi classification): <32 weeks at diagnosis + Doppler AU with absent / reverse flow or (estimated fetal weight <10 percentile + pulsed Doppler ultrasonography) or (estimated fetal weight <percentile 10 + pulsed uterine artery Doppler). Patient giving written informed consent to participate in the study. Exclusion Criteria: Chromosopathies, genetic alterations or fetal malformations. Diagnostic treatment with low molecular weight heparins, oral anticoagulants or acetylsalicylic acid prior to inclusion. History of heparin-induced thrombocytopenia. Active hemorrhage or increased risk of bleeding due to changes in hemostasis. Severe hepatic or pancreatic function disorder. Organic lesions that may bleed (eg, active peptic ulcer, hemorrhagic stroke, aneurysms, or brain tumors).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, double-blind, two-parallel, placebo-controlled, phase III multicenter clinical trial.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>Treatment with low molecular weight Heparin. | Drug: Low molecular weight heparin<br>* Patients included in this study group will receive 3,500 IU / 0.2 ml / day of Bemiparina sc, from inclusion to delivery (estimated median of 5-6 weeks, with a maximum of 13 weeks).<br>* Other names: heparin;|
| Placebo Comparator: Control Group<br>Treatment with Placebo. | Drug: Placebos<br>* Patients included in this study group will placebo (same presentation as the active drug), from inclusion to delivery (estimated median of 5-6 weeks, with a maximum of 13 weeks).<br>* Other names: sodium chloride (0.9%);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of low molecular weight heparin in the prolongation of gestation. | Measured as gestational age (weeks) at birth (dated by ultrasonography <14 weeks by measurement of caudal skull length). | 13 weeks maximum | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of low molecular weight heparin in reducing neonatal morbidity | Measured as the presence of one or more of the following: Perinatal mortality (> 22 weeks of gestation - <28 days postpartum), Significant neonatal morbidity (convulsions, intraventricular haemorrhage> grade III, periventricular leukomalacia, hypoxic-ischemic encephalopathy, abnormal electroencephalogram, necrotizing enterocolitis, acute renal failure (serum creatinine> 1.5 mg / dL) or cardiac failure (requiring inotropic agents), Perinatal mortality (22 weeks to 28 postnatal days), Biomarkers. | 13 weeks maximum | 
| Demonstrate that low molecular weight heparin improves the pro-angiogenic and anti-inflammatory profile. | Measured as the presence of one or more of the following: mother blood biomarkers (sFlt and PlGF), biomerkers, umbilical cord blood biomarkers (TNF alfa, IL6, IFN gamma, FGF basic, VEGF and PlGF), mRNA in trophoblast.( IL6, INFg, TNF alfa, VEGFA, VEGFB, FGF2 y RQVEGF). | 13 weeks maximum | 
| Efficacy of low molecular weight heparin in reducing thrombotic and ischemic placental lesions | Measured as the presence of one or more of the following: Intrauterine growth retardation (Neonatal weight below the 10th percentile of our population + umbilical artery pulsatility index during the third trimester (on two separate occasions> 48h) above the 95th percentile), Preeclampsia, Gestational age (weeks) at birth, Premature delivery before 34 weeks of gestation, Urgent cesarean section due to loss of fetal well-being, Neonatal weight, Neonatal acidosis (arterial pH <7.10 + EB> 12mEq / L), Days stay in the Neonatal Intensive Care Unit, mRNA in trophoblast. | 13 weeks maximum |