Clinical trial NCT01019655: Heparin for Pregnant Women With Thrombophilia
Official title: Low Molecular Weight Heparin for Pregnant Women With Thrombophilia: a Prospective, Randomized, Open Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Pregnancy and Thrombophilia
Keywords: thrombophilia
pregnancy
heparin
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2009-11-25
Enrollment: 300
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: composite endpoint: pregnancy-associated thrombosis/thromboembolism, miscarriage, preeclampsia, intrauterine growth retardation
timeFrame: 10.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Obstetrics and Gynecology
Study officials:
affiliation: University of Vienna
name: Clemens B Tempfer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2021 Mar 29;3(3):CD001689. doi: 10.1002/14651858.CD001689.pub4.
citation: Bennett SA, Bagot CN, Arya R. Pregnancy loss and thrombophilia: the elusive link. Br J Haematol. 2012 Jun;157(5):529-42. doi: 10.1111/j.1365-2141.2012.09112.x. Epub 2012 Mar 26.