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Enrolling by invitationNCT03244020Updated Oct 3, 2025

LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology

A Phase 4 interventional study of Aspirin 325mg and Enoxaparin 40Mg/0.4mL Prefilled Syringe in Sarcoma, Soft Tissue Sarcoma and Bone Sarcoma, sponsored by Massachusetts General Hospital. Enrolling by invitation at 10 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-03.

Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
2,868
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Sarcoma
  • Soft Tissue Sarcoma
  • Bone Sarcoma
  • Bone Metastases
  • Venous Thromboembolism
  • Hematoma
  • Anticoagulant-induced Bleeding
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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.

04

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
2,868 participants (estimated)

Study arms

  • 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

  • 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

  • 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

  • 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

  • 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

  • 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

Interventions

  • DrugAspirin 325mg

    Aspirin 325 mg by mouth once daily

    Also known as: ASA

  • DrugEnoxaparin 40Mg/0.4mL Prefilled Syringe

    Enoxaparin 40 mg subcutaneous injection once daily

    Also known as: Lovenox

05

What researchers measure

Primary outcomes

  1. Venous thromboembolism

    Deep venous thrombosis; pulmonary embolus

    Time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively

Secondary outcomes

  1. Hematoma formation

    Time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively

  2. Complication requiring return to operating room

    Return to operating room for any reason related to the original surgery

    Time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively

  3. Early chemoprophylaxis stop

    ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason

    Time frame: Up to 4 weeks post operatively

  4. Infection

    Infection requiring any sort of treatment (antibiotics alone, return to operating room)

    Time frame: Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively

06

Study locations

10 sites
  • University of California Los Angeles Health
    Los Angeles, California 90404, United States
  • Moffitt Cancer Center
    Tampa, Florida 33612, United States
  • Louisiana State University Health
    New Orleans, Louisiana 70112, United States
  • Johns Hopkins University
    Baltimore, Maryland 21287, United States
  • Santiago Lozano-Calderon
    Boston, Massachusetts 02114, United States
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
  • University of Missouri-Columbia Cancer Care
    Columbia, Missouri 65201, United States
  • Cooper University Health Care
    Camden, New Jersey 08103, United States
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03244020
Lead sponsor
Massachusetts General Hospital
Collaborators
Johns Hopkins University, University of Missouri-Columbia
Responsible party
Santiago Lozano-Calderon (Associate Professor of Orthopaedic Surgery, Massachusetts General Hospital) — Principal investigator
First posted
Aug 9, 2017
Start date
Feb 16, 2018
Primary completion
Dec 31, 2027 (estimated)
Completion
Jul 1, 2028 (estimated)
Last update
Oct 3, 2025

Study contacts

Santiago A Lozano-Calderon, MD, PhD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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