Clinical trial NCT01068795: Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome
Official title: Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Fetal Demise
Fetal Growth Restriction
Preeclampsia
Abruptio Placentae
Thromboembolism
Keywords: placental syndrome
maternal thromboembolic event
enoxaparin
anti-factor Xa
Lead sponsor: HaEmek Medical Center, Israel
Sponsor class: OTHER
First posted: 2010-02-15
Enrollment: 144
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The risk of venous thromboembolism increases in pregnancy. Thrombophilia whether genetic or acquired, is a hypercoagulable disorder that may increase the risk of venous thromboembolic events. Clinically, these events are presented as maternal deep vein thrombosis and pulmonary emboli. Thrombophilias are also associated with adverse fetal outcomes including intrauterine growth restriction, intrauterine fetal death, severe preeclampsia, placental abruption and recurrent abortions.

Pregnant women who experienced one or more of the above complications are advised to be examined for the presence of the genetic or the acquired form of thrombophilia.

Low molecular weight heparin prophylaxis, an anticoagulant, is advised for pregnant women with a history of thromboembolism, and many experts recommend prophylaxis for pregnant patients with a known thrombophilia and history of adverse pregnancy outcomes associated with these hypercoagulable states.

Physiologic changes in normal pregnancy, including weight gain, increased renal clearance and volume of distribution, may decrease the availability of low molecular weight heparin (Enoxaparin or Dalteparin), or produce a less predictable response in pregnant women compared with nonpregnant women. There are no clear recommendations for use of prophylactic low molecular weight heparin in pregnancy. Clinicians tend to use doses suggested for nonpregnant patients. Regarding pregnant patients taking enoxaparin or dalteparin, the American College of Obstetricians and Gynecologists states that "because of the lack of data regarding adequate dosing during pregnancy, anti-factor Xa levels may be monitored".

Two recently published studies demonstrated that plasma anti-factor Xa levels during pregnancy were lower than expected, indicating that many pregnant patients may receive a subprophylactic dosing.

Our objective is to check pregnancy outcome among thrombophilic women treated with an adjusted enoxaparin thromboprophylaxis dosage according to anti-factor Xa plasma levels compared to women with fixed dosage.


Eligibility criteria: Inclusion Criteria:

WOMEN WITH

* Singleton gestation
* A history of fetal demise, fetal growth restriction, placental abruption, preeclampsia, recurrent abortions or maternal thromboembolic event.
* Acquired or congenital thrombophilia treated with low molecular weight heparin

Exclusion Criteria:

* Women treated empirically with low molecular weight heparin
* Women with a history of pregestational diabetes.
* Significant polyhydramnios or oligohydramnios, major fetal structural, generic or chromosomal malformations

Primary outcomes:
measure: placental syndrome or thromboembolic event
timeFrame: 9 months
Secondary outcomes:
measure: enoxaparin side effects
timeFrame: 9 months
Other outcomes:
Locations:
city: Afula
country: Israel
facility: Dep. OB/GYN, HaEmek Medical Center
Study officials:
affiliation: Dep. OB/GYN, HaEmek Medical Center, Afula, Israel
name: Raed Salim, 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: Salim R, Nachum Z, Gavish I, Romano S, Braverman M, Garmi G. Adjusting enoxaparin dosage according to anti-FXa levels and pregnancy outcome in thrombophilic women. A randomised controlled trial. Thromb Haemost. 2016 Sep 27;116(4):687-95. doi: 10.1160/TH16-03-0221. Epub 2016 Jul 21.