Low Weight Heparin prOphylaxis for Placental-Mediated Complications of PrEgnancy

Study Overview
=================
Brief Summary
-----------------
This is a Multicenter, randomized, open-label, parallel groups study to test the hypothesis that prophylactic low molecular weight heparin (LMWH) (enoxaparin) initiated before 14 weeks of gestation could improve maternal and perinatal outcome in women at high risk for developing placental-mediated pregnancy complications.

Official Title
-----------------
Enoxaparin for the Prevention of Placental-Mediated Complications of Pregnancy in Women With Obstetric History or Abnormal Uterine Artery Doppler at First Trimester Ultrasound and Without Thrombophilia: a Multicenter Randomized Controlled Trial

Conditions
-----------------
High Risk Pregnant Women, Placental Insufficiency, Preeclampsia

Intervention / Treatment
-----------------
* Drug: Enoxaparin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women ≥18 years Gestational age < 14 weeks at randomisation One or more of the following complications in a previous pregnancy: Severe PE resulting in delivery before 32 weeks of gestation Newborn weight less than the 10th percentile and documented abnormal Doppler in the umbilical artery during pregnancy before 32 weeks gestation Abruption of placenta Unexplained intrauterine death between 20-41,6 weeks of gestation secondary of placental insufficiency or Uterine arteries Pulsatility Index (mPI) Doppler ≥95th percentile at 11-14 weeks of gestation. Exclusion Criteria: Multiple pregnancy Abnormal thrombophilia study Alcohol or illicit drug use Severe fetal malformations or chromosomal abnormalities Previous history of infertility ( 3 or more early miscarriages) Maternal HIV, Cytomegalovirus or toxoplasma infection Known fetal abnormality or chromosomal defect at randomisation Women with previous venous or arterial thrombotic event Organic lesions that could increase the hemorrhagic risk: gastric ulcus, stroke, a recent hemorrhagic event, high risk situations for hemorrhagic event Known allergy to heparin or LMWH, thrombopenia or thrombosis episode due to heparin treatment Contraindication to LMWH An absolute indication for anticoagulant therapy: venous deep thrombosis, pulmonary embolism, ovaric hyperestimulation, cardiophaty, others Metabolic disorders a risk for development of PE and/or IUGR: Type I diabetes, hipertiroidism, chronic renal insufficiency

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enoxaparin<br>Subcutaneous administration of one dose daily of enoxaparin | Drug: Enoxaparin<br>* 40 mg (4000 IU) women <80 kg at the time of randomization or 60 mg (6000 IU) women> 80 kg at the time of randomization One dose daily. Subcutaneous administration. Treatment periods: the same day of the Initiation visit (from 9 to 13.6 weeks of gestation) until 36 weeks gestation.<br>|
| No Intervention: expectant management<br>Usual management | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of any of these complications of placental insufficiency | Development of any of these complications of placental insufficiency: preeclampsia, intrauterine growth restriction, abruption placentae, and/or intrauterine fetal demise | from date of randomization until the date of delivery (assessed up to 30 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gestational age at birth | Gestational age at birth | from date of randomization until the date of delivery (assessed up to 30 weeks) | 
| Days of hospitalization during pregnancy | Days of hospitalization during pregnancy | from randomization to the time of delivery (30 weeks) | 
| Days of maternal hospitalization in the postpartum period | Days of maternal hospitalization in the postpartum period | from delivery until discharge (an expected average of one week) | 
| Neonatal Data | weight, height, head circumference, Apgar score 1-5 min, arterial pH, venous base excess (BE) of umbilical cord gases, and complications | after the delivery (an expected average of one month) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pregnancy, Preeclampsia, Placental insufficiency