LMWH vs Aspirin for VTE Prophylaxis in Orthopaedic Oncology

Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03244020
• Other study ID #: 2017P000382
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: February 16, 2018
• Est. completion date: July 1, 2028

Study information

• Verified date: April 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1434
• Est. completion date: July 1, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Aspirin 325mg
Aspirin 325 mg by mouth once daily
• Enoxaparin 40Mg/0.4mL Prefilled Syringe
Enoxaparin 40 mg subcutaneous injection once daily

Locations

Country	Name	City	State
United States	Santiago Lozano-Calderon	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Hematoma formation		Up to 3 or 6 months post operatively for bone/soft tissue sarcomas and metastatic osseous disease, respectively
Secondary	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
Secondary	Early chemoprophylaxis stop	ASA or LMWH stopped prior to 4 weeks post operatively by surgeon for any reason	Up to 4 weeks post operatively
Secondary	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