Heparin for Pregnant Women With Thrombophilia

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate whether heparin is an effective treatment in pregnant women at risk for thrombosis and other pregnancy-associated complications.

Detailed Description
-----------------
Women with thrombophilia, i.e. carriage of a factor V leiden mutation, a factor II prothrombin G20210A mutation or a reduced amount of antithrombin III, protein C or protein S, are at elevated risk for thrombosis and related sequelae. Specifically, pregnant women with thrombophilia are at risk for pregnancy-associated thrombosis, pregnancy-associated thromboembolism as well as early miscarriage (until 20 weeks gestation) late miscarriage (after 20 weeks gestation), preeclampsia, and intrauterine growth retardation <10th percentile. Uncontrolled retrospective and prospective studies indicate that a therapy with unfractionated heparin or low molecular weight heparin in pregnancy significantly reduces these pregnancy complications and improves maternal and fetal outcome. The use of low molecular weight heparin in pregnancy is safe with complication rates between 1% and 3%, mainly thrombocytopenia and bleeding complications. Randomized trials to adequately assess the safety and efficacy of heparin in pregnant women with thrombophilia are not available to date. Thus, we intend to randomize pregnant women with thrombophilia during weeks of gestation 11 to 14 into a therapy with nadroparin calcium (fraxiparin®) 0.3 mL daily during pregnancy and six weeks post partum and usual care. The primary end point of this study is a composite endpoint of pregnancy-associated thrombosis, pregnancy-associated thromboembolism, early miscarriage (until 20 weeks gestation) late miscarriage (after 20 weeks gestation), preeclampsia, and intrauterine growth retardation <10th percentile. We hypothesize that a prophylactic therapy with nadroparin calcium will significantly reduce pregnancy complications in pregnant women with thrombophilia.

Official Title
-----------------
Low Molecular Weight Heparin for Pregnant Women With Thrombophilia: a Prospective, Randomized, Open Trial

Conditions
-----------------
Pregnancy and Thrombophilia

Intervention / Treatment
-----------------
* Drug: Nadroparin calcium


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pregnant women with a singleton pregnancy Age >18 years Ability to understand informed consent form Exclusion Criteria: Allergy/hypersensitivity for nadroparin calcium Heparin-associated thrombocytopenia Organ lesions at risk for bleeding such as acute stomach/bowel ulcers, cerebral hemorrhage, cerebral aneurysm uncontrolled hypertension Liver and/or renal dysfunction Known hematologic disease

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 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: Nadroparin calcium<br>nadroparin calcium (fraxiparin®) 0.3 mL daily during pregnancy and six weeks post partum | Drug: Nadroparin calcium<br>* nadroparin calcium (fraxiparin®) 0.3 mL daily during pregnancy and six weeks post partum<br>* Other names: Fraxiparin; code number EU:1-21067;|
| No Intervention: Control<br>No intervention other than usual care at the study site | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| composite endpoint: pregnancy-associated thrombosis/thromboembolism, miscarriage, preeclampsia, intrauterine growth retardation |  | 10.5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
heparin, thrombophilia, pregnancy