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Pregnant and recently postpartum women are at significantly higher risk of developing a blood clot in their arms or legs known as a deep venous thrombosis (DVT) and/or a blood clot in their lungs known as a pulmonary embolism (PE) compared to their non pregnant counterparts. It is estimated that this risk increases anywhere from 4 to 50 times higher in pregnant versus non-pregnant women and further increases almost 11 fold in the post partum period. This risk is almost doubled when the patient undergoes cesarean delivery. In 2011, the American College of Obstetricians and Gynecologists (ACOG) issued updated guidelines stating that for patients undergoing cesarean delivery with additional risk factors for clot or thromboembolism, protective (prophylactic) treatment with low molecular weight heparin (LMWH) a type of blood thinner should be considered. However, no specific guidelines about which risk factors should be considered, or what medication doses should be used were provided. The American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines published in 2012 delineated who should be given prophylaxis based on various risk factors, however acknowledged that the recommendations were based on weak quality evidence.
ACOG endorses either once or twice a day dosing for high risk patients after delivery and states that adjustments for obese women should be made on a case by case basis. However, there are limited studies on the dosing of LMWH in specific subpopulations including post operative patients, pregnant patients and obese patients. All of these studies have urged further investigation of the correct dosing for these high risk subjects due to changes associated with pregnancy and the level of medication in the blood that may put these patients at higher risk of venous thromboembolism. Many previous studies have shown that women in these high risk categories do not achieve protective levels of the medication measured with a laboratory test; anti Xa level. The investigators hypothesize that due to their dual risk, obese post-operative recently pregnant women may not be adequately protected with the daily fixed dose and might need more frequent dosing to protect them.
The objective of this study is to assess what proportion of women achieve the desired anti Xa level with the fixed daily dose versus twice daily weight based dosing (0.5 mg/kg).
This is a multi-center, prospective, randomized controlled study to compare the proportion of patients that achieve the desired effect of LMWH (enoxaparin) thromboprophylaxis as measured by peak anti Xa level with weight based twice daily dosing versus standard fixed daily dosing. The investigators hypothesize that when enoxaparin is dosed by maternal weight and administered twice daily, the anti-factor Xa level would more frequently achieve prophylactic levels when compared to taking a fixed 40 mg of the drug daily.
Subjects will be women with a BMI > 35 who have undergone a cesarean delivery and who will receive thromboprophylaxis with enoxaparin (Lovenox) at the judgment of their physician.
Women who are eligible and consent to participate in the study will be randomized in a 1:1 ratio to one of the following groups:
Group 1 will receive the weight based dosing (0.5mg/kg BID) enoxaparin (Lovenox®; Aventis Pharmaceuticals) regimen Group 2 will received the fixed dose (40mg daily) enoxaparin (Lovenox®; Aventis Pharmaceuticals) regimen.
Treatment will begin between 8 and 12 hours post operatively and this regimen will continue until discharge from the hospital, usually on the third or fourth day after surgery. A single peak anti Xa level will be drawn 3.5-4 hours after the third dose of medication. The results of the anti Xa level will only be for research purposes and will not guide clinical management.
The primary outcome for this study is to assess the peak anti-factor Xa level in the blood, and whether or not the subject achieved the desired prophylactic level when receiving fixed dose of enoxaparin compared with weight based dosing.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Enoxaparin Once Daily | Active Comparator | This arm will have patients randomized to receive 40 mg sub-cutaneous injection of Lovenox (enoxaparin) once daily. |
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| Enoxaparin Twice Daily | Active Comparator | This arm will have patients randomized to receive weight based (0.5 mg/kg) sub-cutaneous injection of Lovenox (enoxaparin) twice daily. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin | Drug | Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. |
| Measure | Description | Time Frame |
|---|---|---|
| Anti Xa Level | Our primary outcome will be to assess the Anti Xa level drawn 3.5-4 hours after the third dose of Lovenox (enoxaparin) to assess if this is in the prophylactic range. | 3.5-4 hours after the third dose of Lovenox (enoxaparin) |
| Measure | Description | Time Frame |
|---|---|---|
| Supraprophylactic Range Anti Xa Level | We will assess if any of the subjects has an Anti Xa level that is in the supraprophylactic range (treatment range). | 3.5-4 hours after the third dose of Lovenox (enoxaparin) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jennifer McNulty, MD | Memorial Care Health System | Principal Investigator |
| Megan L Stephenson, MD | Memorial Health Care System; University of California Irvine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Beach Memorial Care Center for Women at Miller Children's Hospital Long Beach and Long Beach Memorial Hospital | Long Beach | California | 90806 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33779986 | Derived | 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. | |
| 26658126 | Derived | Stephenson ML, Serra AE, Neeper JM, Caballero DC, McNulty J. A randomized controlled trial of differing doses of postcesarean enoxaparin thromboprophylaxis in obese women. J Perinatol. 2016 Feb;36(2):95-9. doi: 10.1038/jp.2015.130. Epub 2015 Dec 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Enoxaparin Once Daily | This arm will have patients randomized to receive 40 mg sub-cutaneous injection of Lovenox (enoxaparin) once daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| FG001 | Enoxaparin Twice Daily | This arm will have patients randomized to receive weight based (0.5 mg/kg) sub-cutaneous injection of Lovenox (enoxaparin) twice daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Enoxaparin Once Daily | This arm will have patients randomized to receive 40 mg sub-cutaneous injection of Lovenox (enoxaparin) once daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. |
| BG001 | Enoxaparin Twice Daily | This arm will have patients randomized to receive weight based (0.5 mg/kg) sub-cutaneous injection of Lovenox (enoxaparin) twice daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Anti Xa Level | Our primary outcome will be to assess the Anti Xa level drawn 3.5-4 hours after the third dose of Lovenox (enoxaparin) to assess if this is in the prophylactic range. | Posted | Mean | 95% Confidence Interval | IU/mL | 3.5-4 hours after the third dose of Lovenox (enoxaparin) |
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| Secondary | Supraprophylactic Range Anti Xa Level | We will assess if any of the subjects has an Anti Xa level that is in the supraprophylactic range (treatment range). | Posted | Number | participants | 3.5-4 hours after the third dose of Lovenox (enoxaparin) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Enoxaparin Once Daily | This arm will have patients randomized to receive 40 mg sub-cutaneous injection of Lovenox (enoxaparin) once daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. | 0 | 42 | 0 | 42 | ||
| EG001 | Enoxaparin Twice Daily | This arm will have patients randomized to receive weight based (0.5 mg/kg) sub-cutaneous injection of Lovenox (enoxaparin) twice daily. Enoxaparin: Enoxaparin will be given in either once daily or twice daily doses. One arm will receive 40 mg enoxaparin subcutaneous injection daily. The other arm will receive 0.5 mg/kg dosed subcutaneously twice daily. This medication will be started 8-12 hours after cesarean section and will be continued while the patient is admitted. It will be stopped at the time of discharge. | 0 | 42 | 0 | 42 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jennifer McNulty | Memorial Care | 562-933-2730 | jjmcnulty@sbcglobal.net |
| ID | Term |
|---|---|
| D009765 | Obesity |
| D009767 | Obesity, Morbid |
| D054556 | Venous Thromboembolism |
| D011655 | Pulmonary Embolism |
| D020246 | Venous Thrombosis |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D013923 | Thromboembolism |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D004617 | Embolism |
| D013927 | Thrombosis |
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| ID | Term |
|---|---|
| D017984 | Enoxaparin |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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| >=65 years |
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| Male |
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| Units | Counts |
|---|---|
| Participants |
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