LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Sarcoma; Soft Tissue Sarcoma; Venous Thromboembolism; Bone Metastases; Hematoma; Bone Sarcoma; Anticoagulant-induced Bleeding
• Intervention / Treatment: Drug: Enoxaparin 40Mg/0.4mL Prefilled Syringe; Drug: Aspirin 325mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 2868
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90404
      • University of California Los Angeles Health
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Santiago Lozano-Calderon
  • Missouri
    • Columbia, Missouri, United States, 65201
      • University of Missouri-Columbia Cancer Care
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper University Health Care
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Patients will first be evaluated for inclusion in a master observational study with the following inclusion criteria:

1. Age ≥18 years
2. Prior or planned surgery on the pelvis or lower extremity

3. Fulfills one of the following:

   a. Cohort A: Metastatic osseous disease, undergoing: i. Endoprosthetic reconstruction ii. Curettage, cement packing, and fixation with nails, plates, and/or screws iii. Intramedullary nail fixation only b. Cohort B: Primary bone sarcoma, undergoing wide resection, amputation, or reconstruction with endoprosthesis, allograft, or allograft-prosthesis composite (APC).

   c. Cohort C: Primary soft tissue sarcoma ≥5 cm in diameter, undergoing wide resection

4. Anticoagulation therapy was received or is planned.

In addition to fulfilling all the inclusion criteria in Part 1 of this study, participants must also not meet any of the below exclusion criteria in order to be eligible for randomization to either aspirin or LMWH.

Exclusion Criteria:

1. Documented prior history of VTE.
2. Preoperative use of therapeutic or prophylactic chemical anticoagulation at the time of surgery.
3. Documented allergy/adverse reaction to either of the two study drugs.
4. Presence of inferior vena cava (IVC) filter.
5. Known, diagnosed hypercoagulable state (other than malignancy).
6. Inability to receive chemical anticoagulation.
7. Preoperative use of full-strength aspirin 325 mg daily; patients already taking aspirin 81 mg daily will not be excluded.
8. Inability for the patient him/herself to give informed consent due to delirium, dementia, or any other reason.
9. Pregnancy
10. Fear of needles that prevents administration of LMWH.
11. Inability to administer medications via needles.
12. For patients with metastatic osseous disease, a Khorana score of ≥3.

Pregnancy testing, via a urine or blood test, is a routine part of pre-operative laboratory testing in patients scheduled to undergo orthopaedic surgeries. Attending surgeons may also choose to exclude any patient from randomization at their discretion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LMWH for Soft Tissue Sarcoma; 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; Enoxaparin 40 mg subcutaneous injection once daily; Other Names: Lovenox
Experimental: ASA for Soft Tissue Sarcoma; 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; Aspirin 325 mg by mouth once daily; Other Names: ASA
Experimental: LMWH for Primary Bone Tumor; 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; Enoxaparin 40 mg subcutaneous injection once daily; Other Names: Lovenox
Experimental: ASA for Primary Bone Tumor; 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; Aspirin 325 mg by mouth once daily; Other Names: ASA
Experimental: LMWH for Metastatic Disease; 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; Enoxaparin 40 mg subcutaneous injection once daily; Other Names: Lovenox
Experimental: ASA for Metastatic Disease; 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; Aspirin 325 mg by mouth once daily; Other Names: ASA

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Johns Hopkins University; University of Missouri-Columbia
• Investigators: Principal Investigator: Santiago A Lozano-Calderón, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2018
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: August 5, 2017
• First Submitted That Met QC Criteria: August 5, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Hemorrhage; Embolism and Thrombosis; Neoplasms, Connective and Soft Tissue; Thromboembolism; Pathological Conditions, Signs and Symptoms; Sarcoma; Hematoma; Venous Thromboembolism; Bone Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Salicylates; Hydroxybenzoates; Aspirin; Enoxaparin
• Other Study ID Numbers: 2017P000382

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes