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

NCT ID: NCT01068795

Last Updated: 2016-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2015-08-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

enoxaparin fixed

enoxaparin dosage will be fixed during pregnancy

Group Type: NO_INTERVENTION

No interventions assigned to this group

enoxaparin adjusted

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

Group Type: EXPERIMENTAL

enoxaparin

Intervention Type: DRUG

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

Interventions

enoxaparin

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

HaEmek Medical Center, Israel

OTHER

Sponsor Role: lead

Responsible Party

Raed Salim

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raed Salim, MD

Role: PRINCIPAL_INVESTIGATOR

Dep. OB/GYN, HaEmek Medical Center, Afula, Israel

Locations

Dep. OB/GYN, HaEmek Medical Center

Afula, , Israel

Countries

Israel

References

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.

Reference Type: DERIVED

PMID: 33779986 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 27440463 (View on PubMed)

Other Identifiers

0048-09-EMC

Identifier Type: -

Identifier Source: secondary_id

0048-09-EMC ANTIXA-02

Identifier Type: -

Identifier Source: org_study_id