Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome
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Purpose
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.
| Condition | Intervention |
|---|---|
|
Fetal Demise Fetal Growth Restriction Preeclampsia Abruptio Placentae Thromboembolism |
Drug: enoxaparin |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention |
| Official Title: | Dose Adjusting Enoxaparin Thromboprophylaxis Dosage According to Anti-factor Xa Plasma Levels Improve Pregnancy Outcome |
- placental syndrome or thromboembolic event [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- enoxaparin side effects [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 144 |
| Study Start Date: | July 2009 |
| Estimated Study Completion Date: | July 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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
enoxaparin dosage will be adjusted according to anti-factor Xa plasma levels
|
Eligibility| Ages Eligible for Study: | 18 Years to 45 Years |
| Genders Eligible for Study: | 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:
- 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
Contacts and Locations| Contact: Raed Salim, MD | 97246494031 | salim_ra@clalit.org.il |
| Israel | |
| Dep. OB/GYN, HaEmek Medical Center | Recruiting |
| Afula, Israel | |
| Contact: Raed Salim, MD salim_ra@clalit.org.il | |
| Principal Investigator: Raed Salim, MD | |
| Principal Investigator: | Raed Salim, MD | Dep. OB/GYN, HaEmek Medical Center, Afula, Israel |
More Information
No publications provided
| Responsible Party: | Raed Salim, MD, HaEmek Medical Center, Israel |
| ClinicalTrials.gov Identifier: | NCT01068795 History of Changes |
| Other Study ID Numbers: | 0048-09-EMC ANTIXA-02, 0048-09-EMC |
| Study First Received: | January 20, 2010 |
| Last Updated: | March 19, 2013 |
| Health Authority: | Israel: The Israel National Institute for Health Policy Research and Health Services Research |
Keywords provided by HaEmek Medical Center, Israel:
|
placental syndrome maternal thromboembolic event enoxaparin anti-factor Xa |
Additional relevant MeSH terms:
|
Abruptio Placentae Fetal Growth Retardation Pre-Eclampsia Thromboembolism Obstetric Labor Complications Pregnancy Complications Placenta Diseases Fetal Diseases Growth Disorders Pathologic Processes Hypertension, Pregnancy-Induced Embolism and Thrombosis |
Vascular Diseases Cardiovascular Diseases Thrombosis Enoxaparin Anticoagulants Hematologic Agents Therapeutic Uses Pharmacologic Actions Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents |
ClinicalTrials.gov processed this record on June 17, 2013