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

NCT01068795 | Completed DMC

• 2 other identifiers: 0048-09-EMC ANTIXA-020048-09-EMC
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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

Keywords

placental syndrome; maternal thromboembolic event; enoxaparin; anti-factor Xa

Outcome Measures

Primary Outcomes (1)

• placental syndrome or thromboembolic event

  9 months

Secondary Outcomes (1)

• enoxaparin side effects

  9 months

Study Arms (2)

enoxaparin fixed

NO INTERVENTION

enoxaparin dosage will be fixed during pregnancy

enoxaparin adjusted

EXPERIMENTAL

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

Drug: enoxaparin

Interventions

enoxaparin DRUG

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

enoxaparin adjusted

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HaEmek Medical Center, Israel: lead

Study Sites (1)

Dep. OB/GYN, HaEmek Medical Center

Afula, Israel

Location

Related Publications (2)

• 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.

  PMID: 33779986 DERIVED

• 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.

  PMID: 27440463 DERIVED

MeSH Terms

Conditions

Fetal Death; Fetal Growth Retardation; Pre-Eclampsia; Abruptio Placentae; Thromboembolism

Interventions

Enoxaparin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fetal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Growth Disorders; Hypertension, Pregnancy-Induced; Obstetric Labor Complications; Placenta Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Raed Salim, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 20, 2010
• First Posted: February 15, 2010
• Study Start: July 1, 2009
• Primary Completion: January 1, 2015
• Study Completion: August 1, 2015
• Last Updated: February 23, 2016

Record last verified: 2016-02

Locations

IL (1)