Low Molecular Weight Heparin (LMWH) vs Aspirin for Venous Thromboembolism (VTE) Prophylaxis in Orthopaedic Oncology

Study Overview
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Brief Summary
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Aspirin and low molecular weight heparin (LMWH) are both commonly employed pharmacologic methods of venous thromboembolism (VTE) prophylaxis after orthopaedic surgery. Data comparing these two methods of VTE prophylaxis in patients undergoing pelvic/lower extremity orthopaedic surgery for malignancy are lacking, however, as compared to the data and guidelines present for VTE chemoprophylaxis after joint arthroplasty and hip fracture surgery. In this clinical trial, our specific aim is to compare the post operative incidence of VTE between patients receiving aspirin and LMWH after pelvic/lower extremity orthopaedic oncology procedures.

Detailed Description
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Lower extremity orthopaedic surgery and malignancy are both known major risk factors for venous thromboembolism (VTE). Guidelines from high quality data exist with regards to VTE prophylaxis in patients undergoing orthopaedic surgery, particularly joint arthroplasty. Far fewer data are available regarding the efficacy of various methods of pharmacologic VTE prophylaxis in patients undergoing surgery for primary or metastatic musculoskeletal malignancies as malignancy itself is known to confer a hypercoagulable state. The existing data, including published data from our institution, are almost exclusively from retrospective studies. Given the limited external validity of existing guidelines and limitations inherent in applying data from retrospective studies, a randomized, prospective study comparing two of the most common methods of pharmacologic VTE prophylaxis would help to guide clinical care of this patient population. In addition, large dead spaces susceptible to hematoma formation are often created from tumor resections in orthopaedic oncology. Our retrospective data suggest that hematoma formation may be an independent predictor of infection. An important risk of chemical VTE prophylaxis is an increased incidence of bleeding into these dead spaces, leading to hematomas. This illustrates the complexity of selecting a method of VTE prophylaxis in patients at both high risk of VTE and hematoma formation and the need for high quality data to guide clinical decision-making in this patient population. The specific aim of this study is to compare the post operative incidence of symptomatic deep vein thrombosis (DVT) and pulmonary embolus (PE) between patients who receive low molecular weight heparin (LMWH) versus aspirin for prophylaxis after having undergone pelvic or lower extremity orthopaedic oncology surgery (primary bone sarcomas, soft tissue sarcomas, and metastatic osseous disease). Our secondary aim is to compare the incidence of hematoma formation and wound complications between these methods of pharmacologic prophylaxis in the aforementioned patient population. Our hypothesis is that there is no significant difference in the incidence rate of symptomatic DVT/PE in patients administered LMWH versus aspirin for prophylaxis; however there may exist a difference in the rate of wound complications between these prophylaxis methods.

Official Title
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Low Molecular Weight Heparin Versus Aspirin for Venous Thromboembolism Prophylaxis in Orthopaedic Oncology

Conditions
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Sarcoma, Soft Tissue Sarcoma, Bone Sarcoma, Bone Metastases, Venous Thromboembolism, Hematoma, Anticoagulant-induced Bleeding

Intervention / Treatment
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* Drug: Aspirin 325mg
* Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with metastatic osseous disease of the lower extremities or pelvis treated with endoprosthetic reconstruction, curettage and cement packing with intramedullary nail fixation and/or plate and screws, or intramedullary nail fixation only. Patients with primary bone sarcomas of the lower extremities or pelvis treated with wide resections and amputations or reconstruction with endoprosthesis, allografts, or allograft prosthetic composites. Patients with soft tissue sarcomas of the lower extremities or pelvis measuring more than 8 cm in size, deep to the fascia levels, treated with preoperative or postoperative radiation, plus/minus preoperative and/or postoperative chemotherapy, receiving surgery with wide margins, followed by primary closure, closure with free or rotational, and/or skin graft. (478 patients per arm) Exclusion Criteria: Documented prior history of VTE Pre-operative use of therapeutic or prophylactic chemical anti-coagulation at the time of surgery (not including ASA 81 mg) Documented allergy/adverse reaction to either of the two study drugs Presence of an inferior vena cava (IVC) filter Known diagnosed hypercoagulable state (other than malignancy) Inability to receive chemical anticoagulation Pre-operative use of full strength aspirin 325 milligrams (mg) daily Inability for the patient him/herself to give informed consent due to delirium, dementia, or any other reason. Pregnancy Fear of needles Inability to administer medications via needles themselves Situation in which the attending surgeon does not feel that randomization of a subject would be appropriate

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three separate patient categories are being investigated in this trial. All patients are undergoing pelvic and/or lower extremity surgery for one of three possible conditions: 1) soft tissue sarcoma; 2) primary bone sarcoma; 3) metastatic bone disease. Within each of these groups, patients will be randomized to either aspirin or low molecular weight heparin (enoxaparin) for venous thromboembolism prophylaxis post operatively.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LMWH for Soft Tissue Sarcoma<br>Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis | Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe<br>* Enoxaparin 40 mg subcutaneous injection once daily<br>* Other names: Lovenox;|
| Experimental: ASA for Soft Tissue Sarcoma<br>Patients undergoing surgery for pelvic/lower extremity soft tissue sarcomas and are randomized to aspirin 325 mg po daily for VTE prophylaxis | Drug: Aspirin 325mg<br>* Aspirin 325 mg by mouth once daily<br>* Other names: ASA;|
| Experimental: LMWH for Primary Bone Tumor<br>Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis | Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe<br>* Enoxaparin 40 mg subcutaneous injection once daily<br>* Other names: Lovenox;|
| Experimental: ASA for Primary Bone Tumor<br>Patients undergoing surgery for pelvic/lower extremity primary bone tumor and are randomized to aspirin 325 mg po daily for VTE prophylaxis | Drug: Aspirin 325mg<br>* Aspirin 325 mg by mouth once daily<br>* Other names: ASA;|
| Experimental: LMWH for Metastatic Disease<br>Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to Enoxaparin 40Mg/0.4mL prefilled syringe subcutaneous injection daily for VTE prophylaxis | Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe<br>* Enoxaparin 40 mg subcutaneous injection once daily<br>* Other names: Lovenox;|
| Experimental: ASA for Metastatic Disease<br>Patients undergoing surgery for pelvic/lower extremity metastatic bone disease and are randomized to aspirin 325 mg po daily for VTE prophylaxis | Drug: Aspirin 325mg<br>* Aspirin 325 mg by mouth once daily<br>* Other names: ASA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Venous thromboembolism | Deep venous thrombosis; pulmonary embolus | Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematoma formation |  | Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively | 
| Complication requiring return to operating room | Return to operating room for any reason related to the original surgery | Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively | 
| Early chemoprophylaxis stop | ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason | Up to 4 weeks post operatively | 
| Infection | Infection requiring any sort of treatment (antibiotics alone, return to operating room) | Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively |