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CompletedNCT01068795Updated Feb 23, 2016

Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome

An interventional study of enoxaparin in Fetal Demise, Fetal Growth Restriction and Preeclampsia, sponsored by HaEmek Medical Center, Israel. Completed at 1 site in Israel. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2016-02-23.

Sponsored by HaEmek Medical Center, Israel · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
144
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
Female
01

Study 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.

02

Conditions studied

  • Fetal Demise
  • Fetal Growth Restriction
  • Preeclampsia
  • Abruptio Placentae
  • Thromboembolism

Keywords

  • placental syndrome
  • maternal thromboembolic event
  • enoxaparin
  • anti-factor Xa
03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
144 participants (actual)

Study arms

  • No intervention
    enoxaparin fixed

    enoxaparin dosage will be fixed during pregnancy

  • Experimental
    enoxaparin adjusted

    enoxaparin dosage will be adjusted according to anti-factor Xa plasma levels

    Drug: enoxaparin

Interventions

  • Drugenoxaparin

    enoxaparin dosage will be adjusted according to anti-factor Xa plasma levels

05

What researchers measure

Primary outcomes

  1. placental syndrome or thromboembolic event

    Time frame: 9 months

Secondary outcomes

  1. enoxaparin side effects

    Time frame: 9 months

06

Study locations

1 site
  • Dep. OB/GYN, HaEmek Medical Center
    Afula, Israel
07

References and documents

Publications

  • 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. PubMed 33779986 ↗
  • 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. PubMed 27440463 ↗
08

Registry details

Key details

Study ID
NCT01068795
Lead sponsor
HaEmek Medical Center, Israel
Responsible party
Raed Salim (MD, HaEmek Medical Center, Israel) — Principal investigator
First posted
Feb 15, 2010
Start date
Jul 2009
Primary completion
Jan 2015
Completion
Aug 2015
Last update
Feb 23, 2016

Study contacts

Raed Salim, MD
principal investigator · Dep. OB/GYN, HaEmek Medical Center, Afula, Israel

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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